汉族人群花生四烯酸ω-羟化酶基因编码区多态性位点的研究
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摘要
目的花生四烯酸由细胞色素P450ω-羟化酶催化生成的19-和20-羟烷四烯酸(19-,20-HETE),通过阻断Ca~(2+)激活的K~+通道而使血管平滑肌去极化,产生强有力的血管收缩作用。在血管平滑肌细胞中19-和20-HETE的生成可由血管紧张素Ⅱ、内皮素和去甲肾上腺素刺激,被一氧化氮所抑制。在肾脏可收缩微血管,抑制Na~+-K~+-ATP酶的活性及近曲小管的钠转运,调节水钠重吸收。在多种疾病过程,尤其是高血压病中,扮演着重要角色。编码生成该酶的基因——CYP4A11和CYP4F2已成为研究高血压病新的候选基因。而对这两个基因的结构及多态性情况,尤其是与心血管疾病的联系,知之甚少。寻找人群中这两个基因编码区的多态性位点分布情况,可以为研究高血压病的基因机制提供新的依据。
方法采集50例血压正常、无血缘关系的汉族人外周静脉血白细胞;提取基因组DNA;设计特异性引物,PCR法分段扩增基因编码区序列,电泳检测后回收目的片断;测序,与参考序列比对后统计结果。
结果CYP4A11共发现16个多态性位点,其中5个有意义:1个5’端非编码区的突变位点A-54G,4个引起氨基酸改变的多态性位点,分别为A6890C、A7207G、T7394A和T8590C ; CYP4F2共检测到6个多态性位点,其中3个有意义:1个为3’端非编码区的多态性位点G19026A,2个引起氨基酸改变的多态性位点T2013G和G18000A。其余均为内含子区或者同义突变。
结论1.多态性位点存在种族差异;2.突变位点大多数位于内含子区,或者为同义突变,仅有少数有意义;3.发现的多态性位点可能引起蛋白质构象进而改变蛋白质功能,或者引起基因转录活性的改变,并为下面的蛋白质组学研究和大样本人群研究奠定了基础。
Objective Arachidonic acid Cytochrome P450 (CYP)ω-hydroxylases catalyze arachidonic acid to produce 19- and 20-HETE, especially the later. 19- and 20-HETE depolarize VSM by blocking the open-state probability of Ca~(2+)-activated K~+-channels. The formation of 19- and 20-HETE in vascular smooth muscle is enhanced by angiotensin II, endothelin and norepinephrine and is attenuated by nitric oxide (NO). 20-HETE plays an important role in the regulation of sodium reabsorption in renal tubules. 20-HETE inhibits Na~+-K~+-ATPase activity and sodium transport in proximal tubule. Additionally, 20-HETE may involve in a variety of pathophysiological conditions, especially primary hypertension. CYP4A11 and CYP4F2 became new interesting genes for hypertension, though we know little about them. Identification of characteristics single nucleotide polymorphisms (SNPs) existing in coding region of these genes may provide some new insights into the genetic mechanisms of hypertension.
Method Genomic DNA was extracted from blood white cells of 50 unrelated Chinese Han people with normotension. The coding regions were amplified by PCR, respectively. After sequenced, the information wan aligned and summarized.
Results Sixteen SNP sites in CYP4A11 were identified,in which there are 5 sense mutation, including A-54G in 5’-uncoding region, A6890C, A7207G, T7394A and T8590C , which caused corresponding amino acid changing (K-T, S-G, F-Y and F-S), respectively. And in CYP4F2 three of six SNP sites were sense, including G19026A in 3’uncoding region, T2013G and G18000A causing amino substitute (V-G and V-M) , respectively. Others were in intron region or synonymous.
Conclusion This study suggests that multiple variants exist within or near the CYP4A11 and CYP4F2 genes in Chinese populations. Most of variants were nonsense or in intron region. These SNPs or variants may change biologicalactivity ofω-hydroxylases. It may provide some directions for protein research consequently.
方法采集50例血压正常、无血缘关系的汉族人外周静脉血白细胞;提取基因组DNA;设计特异性引物,PCR法分段扩增基因编码区序列,电泳检测后回收目的片断;测序,与参考序列比对后统计结果。
结果CYP4A11共发现16个多态性位点,其中5个有意义:1个5’端非编码区的突变位点A-54G,4个引起氨基酸改变的多态性位点,分别为A6890C、A7207G、T7394A和T8590C ; CYP4F2共检测到6个多态性位点,其中3个有意义:1个为3’端非编码区的多态性位点G19026A,2个引起氨基酸改变的多态性位点T2013G和G18000A。其余均为内含子区或者同义突变。
结论1.多态性位点存在种族差异;2.突变位点大多数位于内含子区,或者为同义突变,仅有少数有意义;3.发现的多态性位点可能引起蛋白质构象进而改变蛋白质功能,或者引起基因转录活性的改变,并为下面的蛋白质组学研究和大样本人群研究奠定了基础。
Objective Arachidonic acid Cytochrome P450 (CYP)ω-hydroxylases catalyze arachidonic acid to produce 19- and 20-HETE, especially the later. 19- and 20-HETE depolarize VSM by blocking the open-state probability of Ca~(2+)-activated K~+-channels. The formation of 19- and 20-HETE in vascular smooth muscle is enhanced by angiotensin II, endothelin and norepinephrine and is attenuated by nitric oxide (NO). 20-HETE plays an important role in the regulation of sodium reabsorption in renal tubules. 20-HETE inhibits Na~+-K~+-ATPase activity and sodium transport in proximal tubule. Additionally, 20-HETE may involve in a variety of pathophysiological conditions, especially primary hypertension. CYP4A11 and CYP4F2 became new interesting genes for hypertension, though we know little about them. Identification of characteristics single nucleotide polymorphisms (SNPs) existing in coding region of these genes may provide some new insights into the genetic mechanisms of hypertension.
Method Genomic DNA was extracted from blood white cells of 50 unrelated Chinese Han people with normotension. The coding regions were amplified by PCR, respectively. After sequenced, the information wan aligned and summarized.
Results Sixteen SNP sites in CYP4A11 were identified,in which there are 5 sense mutation, including A-54G in 5’-uncoding region, A6890C, A7207G, T7394A and T8590C , which caused corresponding amino acid changing (K-T, S-G, F-Y and F-S), respectively. And in CYP4F2 three of six SNP sites were sense, including G19026A in 3’uncoding region, T2013G and G18000A causing amino substitute (V-G and V-M) , respectively. Others were in intron region or synonymous.
Conclusion This study suggests that multiple variants exist within or near the CYP4A11 and CYP4F2 genes in Chinese populations. Most of variants were nonsense or in intron region. These SNPs or variants may change biologicalactivity ofω-hydroxylases. It may provide some directions for protein research consequently.
引文
1. Mayer B, Lieb W, Gotz A, Konig IR, Aherrahrou Z, Thiemig A, Holmer S, Hengstenberg C, Doering A, Loewel H, Hense HW, Schunkert H, Erdmann J: Association of the T8590C polymorphism of CYP4A11 with hypertension in the MONICA Augsburg echocardiographic substudy. Hypertension 2005;46:766-771.
2. Amaral SL, Maier KG, Schippers DN, Roman RJ, Greene AS: CYP4A metabolites of arachidonic acid and VEGF are mediators of skeletal muscle angiogenesis. Am J Physiol Heart Circ Physiol 2003;284:H1528-1535.
3. Kaduce TL, Fang X, Harmon SD, Oltman CL, Dellsperger KC, Teesch LM, Gopal VR, Falck JR, Campbell WB, Weintraub NL, Spector AA: 20-hydroxyeicosatetraenoic acid (20-HETE) metabolism in coronary endothelial cells. J Biol Chem 2004;279:2648-2656.
4. Randriamboavonjy V, Kiss L, Falck JR, Busse R, Fleming I: The synthesis of 20-HETE in small porcine coronary arteries antagonizes EDHF-mediated relaxation. Cardiovasc Res 2005;65:487-494.
5. Omata K, Abraham NG, Schwartzman ML: Renal cytochrome P-450-arachidonic acid metabolism: localization and hormonal regulation in SHR. Am J Physiol 1992;262:F591-599.
6. Oyekan AO, McGiff JC: Functional response of the rat kidney to inhibition of nitric oxide synthesis: role of cytochrome p450-derived arachidonate metabolites. Br J Pharmacol 1998;125:1065-1073.
7. Wang MH, Wang J, Chang HH, Zand BA, Jiang M, Nasjletti A, Laniado-Schwartzman M: Regulation of renal CYP4A expression and 20-HETE synthesis by nitric oxide in pregnant rats. Am J Physiol Renal Physiol 2003;285:F295-302.
8. Sarkis A, Lopez B, Roman RJ: Role of 20-hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids in hypertension. Curr Opin Nephrol Hypertens 2004;13:205-214.
9. Harder DR, Gebremedhin D, Narayanan J, Jefcoat C, Falck JR,Campbell WB, Roman R: Formation and action of a P-450 4A metabolite of arachidonic acid in cat cerebral microvessels. Am J Physiol 1994;266:H2098-2107.
10. Yu M, Cambj-Sapunar L, Kehl F, Maier KG, Takeuchi K, Miyata N, Ishimoto T, Reddy LM, Falck JR, Gebremedhin D, Harder DR, Roman RJ: Effects of a 20-HETE antagonist and agonists on cerebral vascular tone. Eur J Pharmacol 2004;486:297-306.
11. Miyata N, Seki T, Tanaka Y, Omura T, Taniguchi K, Doi M, Bandou K, Kametani S, Sato M, Okuyama S, Cambj-Sapunar L, Harder DR, Roman RJ: Beneficial effects of a new 20-hydroxyeicosatetraenoic acid synthesis inhibitor, TS-011 [N-(3-chloro-4-morpholin-4-yl) phenyl-N'-hydroxyimido formamide], on hemorrhagic and ischemic stroke. J Pharmacol Exp Ther 2005;314:77-85.
12. Takeuchi K, Miyata N, Renic M, Harder DR, Roman RJ: Hemoglobin, NO, and 20-HETE interactions in mediating cerebral vasoconstriction following SAH. Am J Physiol Regul Integr Comp Physiol 2006;290:R84-89.
13. Gainer JV, Bellamine A, Dawson EP, Womble KE, Grant SW, Wang Y, Cupples LA, Guo CY, Demissie S, O'Donnell CJ, Brown NJ, Waterman MR, Capdevila JH: Functional variant of CYP4A11 20-hydroxyeicosatetraenoic acid synthase is associated with essential hypertension. Circulation 2005;111:63-69.
14. Fleming I: Cytochrome P-450 under pressure: more evidence for a link between 20-hydroxyeicosatetraenoic acid and hypertension. Circulation 2005;111:5-7.
15. Cho BH, Park BL, Kim LH, Chung HS, Shin HD: Highly polymorphic human CYP4A11 gene. J Hum Genet 2005;50:259-263.
16. Xu F, Falck JR, Ortiz de Montellano PR, Kroetz DL: Catalytic activity and isoform-specific inhibition of rat cytochrome p450 4F enzymes. J Pharmacol Exp Ther 2004;308:887-895.
17. Parker TA, Grover TR, Kinsella JP, Falck JR, Abman SH: Inhibition of 20-HETE abolishes the myogenic response during NOS antagonism in the ovine fetal pulmonary circulation. Am J Physiol Lung Cell Mol Physiol 2005;289:L261-267.
18. Yu M, Alonso-Galicia M, Sun CW, Roman RJ, Ono N, Hirano H, Ishimoto T, Reddy YK, Katipally KR, Reddy KM, Gopal VR, Yu J, Takhi M, Falck JR: 20-hydroxyeicosatetraenoic acid (20-HETE): structural determinants for renal vasoconstriction. Bioorg Med Chem 2003;11:2803-2821.
19. Quilley J, Qiu Y, Hirt J: Inhibitors of 20-hydroxyeicosatetraenoic acid reduce renal vasoconstrictor responsiveness. J Pharmacol Exp Ther 2003;307:223-229.
20. Bellamine A, Wang Y, Waterman MR, Gainer JV, 3rd, Dawson EP, Brown NJ, Capdevila JH: Characterization of the CYP4A11 gene, a second CYP4A gene in humans. Arch Biochem Biophys 2003;409:221-227.
21. Kikuta Y, Kusunose E, Kusunose M: Prostaglandin and leukotriene omega-hydroxylases. Prostaglandins Other Lipid Mediat 2002;68-69:345-362.
22. Alonso-Galicia M, Maier KG, Greene AS, Cowley AW, Jr., Roman RJ: Role of 20-hydroxyeicosatetraenoic acid in the renal and vasoconstrictor actions of angiotensin II. Am J Physiol Regul Integr Comp Physiol 2002;283:R60-68.
23. Roman RJ, Maier KG, Sun CW, Harder DR, Alonso-Galicia M: Renal and cardiovascular actions of 20-hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids. Clin Exp Pharmacol Physiol 2000;27:855-865.
24. Lasker JM, Chen WB, Wolf I, Bloswick BP, Wilson PD, Powell PK: Formation of 20-hydroxyeicosatetraenoic acid, a vasoactive and natriuretic eicosanoid, in human kidney. Role of Cyp4F2 and Cyp4A11. J Biol Chem 2000;275:4118-4126.
25. Kikuta Y, Kusunose E, Kusunose M: Characterization of human liver leukotriene B(4) omega-hydroxylase P450 (CYP4F2). J Biochem (Tokyo) 2000;127:1047-1052.
26. Kawashima H, Naganuma T, Kusunose E, Kono T, Yasumoto R, Sugimura K, Kishimoto T: Human fatty acid omega-hydroxylase, CYP4A11: determination of complete genomic sequence and characterization of purified recombinant protein. Arch Biochem Biophys 2000;378:333-339.
27. Hoch U, Zhang Z, Kroetz DL, Ortiz de Montellano PR: Structural determination of the substrate specificities and regioselectivities of the rat and human fatty acid omega-hydroxylases. Arch Biochem Biophys 2000;373:63-71.
28. Kikuta Y, Miyauchi Y, Kusunose E, Kusunose M: Expression and molecular cloning of human liver leukotriene B4 omega-hydroxylase (CYP4F2) gene. DNA Cell Biol 1999;18:723-730.
29. Chang YT, Loew GH: Homology modeling and substrate binding study of human CYP4A11 enzyme. Proteins 1999;34:403-415.
30. Powell PK, Wolf I, Jin R, Lasker JM: Metabolism of arachidonic acid to 20-hydroxy-5,8,11, 14-eicosatetraenoic acid by P450 enzymes in human liver: involvement of CYP4F2 and CYP4A11. J Pharmacol Exp Ther 1998;285:1327-1336.
31. Crespi CL, Chang TK, Waxman DJ: Determination of CYP4A11-catalyzed lauric acid 12-hydroxylation by high-performance liquid chromatography with radiometric detection. Methods Mol Biol 1998;107:163-167.
32. Ma YH, Gebremedhin D, Schwartzman ML, Falck JR, Clark JE, Masters BS, Harder DR, Roman RJ: 20-Hydroxyeicosatetraenoic acid is an endogenous vasoconstrictor of canine renal arcuate arteries. Circ Res 1993;72:126-136.
33. Imaoka S, Ogawa H, Kimura S, Gonzalez FJ: Complete cDNA sequence and cDNA-directed expression of CYP4A11, a fatty acid omega-hydroxylase expressed in human kidney. DNA Cell Biol 1993;12:893-899.
1. Alonso-Galicia, M., Sun, C.W., Falck, J.R., Harder, D.R. and Roman, R.J. (1998). Contribution of 20-HETE to the vasodilator actions of nitric oxide in renal arteries. Am. J. Physiol. 275: F370–F378.
2. Alonso-Galicia, M., Falck, J.R., Reddy, K.M. and Roman, R.J. (1999). 20-HETE agonists and antagonists in the renal circulation. Am. J. Physiol. 277: F790–F796.
3. Alonso-Galicia, M., Maier, K.G., Greene, A.S., Cowley, A.W. Jr. and Roman, R.J. (2002). Role of 20- hydroxyeicosatetraenoic acid in the renal and vasoconstrictor actions of angiotensin II. Am. J. Physiol. 283: R60–R68.
4. Amaral, S.L., Maier, K.G., Schippers, D.N., Roman, R.J. and Greene,A.S. (2003). CYP4A metabolites of arachidonic acid and VEGF are mediators of skeletal muscle angiogenesis. Am. J. Physiol. 284: H1528–H1535.
5. Bednar, M.M., Gross, C.E., Balazy, M.K., Belosludtsev, Y., Colella, D.T., Falck, J.R. and Balazy, M. (2000). 16(R)-hydroxy-5, 8, 11, 14- eicosatetraenoic acid, a new arachidonate metabolite in human polymorphonuclear leukocytes. Biochem. Pharmacol. 60: 447–455.
6. Christmas, P., Jones, J.P., Patten, C.J., Rock, D.A., Zheng, Y., Cheng, S.M., Weber, B.M., Carlesso, N., Scadden, D.T., Rettie, A.E. and Soberman, R.J. (2001). Alternative splicing determines the function of CYP4F3 by switching substrate specificity. J. Biol. Chem. 276: 38166–38172.
7. Cambj-Sapunar, L., Yu, M., Harder, D.R. and Roman, R.J. (2003). Contribution of 5-hydroxytryptamine1B receptors and 20-hydroxyeiscosatetraenoic acid to fall in cerebral blood flow after subarachnoid hemorrhage. Stroke 34: 1269–1275.
8. Campbe ll, W. B. , Gebr eme d hin, D., Pratt, P. F. and Harde r , D.R. ( 1996) . Id entif i cation of epoxyeicosatrienoic acids as endothelium-derived hyperpolarizing factors. Circ. Res. 78: 415–425
9. Capdevila, J., Chacos, N., Werringloer, J., Prough, R.A. and Estabrook, R.W. (1981). Liver microsomal cytochrome P-450 and the oxidative metabolism of arachidonic acid. Proc. Natl. Acad. Sci. U.S.A. 78: 5362–5366.
10. Carroll, M.A., Sala, A., Dunn, C.E., McGiff, J.C. and Murphy, R.C. (1991). Structural identification of cytochrome P450-dependent arachidonate metabolites formed by rabbit medullary thick ascending limb cells. J. Biol. Chem. 266: 12306–12312.
11. Carroll, M.A., Balazy, M., Margiotta, P., Huang, D.D., Falck, J.R. and McGiff, J.C. (1996). Cytochrome P-450-dependent HETEs: profile of biological activity and stimulation by vasoactive peptides. Am. J. Physiol. 271: R863–R869.
12. Carroll, M.A., Balazy, M., Huang, D.D., Rybalova, S., Falck, J.R. and McGiff, J.C. (1997). Cytochrome P450-derived renal HETEs: storage and release. Kidney Int. 51: 1696–1702.
13. Chen, P., Guo, M., Wygle, D., Edwards, P.A., Falck, J.R., Roman, R.J. and Scicli, A.G. (2005). Inhibitors of cytochrome P450 4A suppress angiogenic responses. Am. J. Pathol. 166: 615–624.
14. Christmas, P., Jones, J.P., Patten, C.J., Rock, D.A., Zheng, Y., Cheng, S.M., Weber, B.M., Carlesso, N., Scadden, D.T., Rettie, A.E. and Soberman, R.J. (2001). Alternative splicing determines the function of CYP4F3 by switching substrate specificity. J. Biol. Chem. 276: 38166–38172.
15. Croft, K.D., McGiff, J.C., Sanchez-Mendoza, A. and Carroll, M.A. (2000). Angiotensin II releases 20- HETE from rat renal microvessels. Am. J. Physiol. 279: F544–F551.
16. Cui, X., Kawashima, H., Barclay, T.B., Peters, J.M., Gonzalez, F.J., Morgan, E.T. and Strobel, H.W. (2001). Molecular cloning and regulation of expression of two novel mouse CYP4F genes: ex pressi on i n pero xi so me pro l ifera t o r -a ct iv at ed rec e pt or a l p h a - defi ci ent m i c e upo n lipopolysaccharide and clofibrate challenges. J. Pharmacol. Exp. Ther. 296: 542–550.
17. Dahly-Vernon, A.J., Sharma, M., McCarthy, E.T., Savin, V.J., Ledbetter, S.R. and Roman, R.J. (2005). Transforming growth factor-beta, 20-HETE interaction, and glomerular injury in Dahl salt- sensitive rats. Hypertension 45: 643–648.
18. Eckman, D.M., Hopkins, N., McBride, C. and Keef, K.D. (1998). Endothelium-dependent relaxation and hyperpolarization in guinea-pig coronary artery: role of epoxyeicosatrienoic acid. Br. J. Pharmacol. 124: 181–189.
19. Escalante, B., Erlij, D., Falck, J.R. and McGiff, J.C. (1991). Effect of cytochrome P450 arachidonate metabolites on ion transport in rabbit kidney loop of Henle. Science 251: 799–802.
20. Escalante, B., Erlij, D., Falck, J.R. and McGiff, J.C. (1994).Cytochrome P-450 arachidonate metabolites affect ion fluxes in rabbit medullary thick ascending limb. Am. J. Physiol. 266: C1775–C1782.
21. Fisslthaler, B., Popp, R., Kiss, L., Potente, M., Harder, D.R., Fleming, I. and Busse, R. (1999). Cytochrome P450 2C is an EDHF synthase in coronary arteries. Nature 401: 493–497.
22. Fleming, I. (2001). Cytochrome p450 and vascular homeostasis. Circ. Res. 89: 753–762.
23. Fleming, I., Michaelis, U.R., Bredenkotter, D., Fisslthaler, B., Dehghani, F., Brandes, R.P. and Busse, R. (2001). Endothelium-derived hyperpolarizing factor synthase (Cytochrome P450 2C9) is a functionally significant source of reactive oxygen species in coronary arteries. Circ. Res. 88: 44–51.
24. Frisbee, J.C., Roman, R.J., Krishna, U.M., Falck, J.R. and Lombard, J.H. (2001a). 20-HETE modulates myogenic response of skeletal muscle resistance arteries from hypertensive Dahl-SS rats. Am. J. Physiol. 280: H1066–H1074.
25. Frisbee, J.C., Roman, R.J., Falck, J.R., Krishna, U.M. and Lombard, J.H. (2001b). 20-HETE contributes to myogenic activation of skeletal muscle resistance arteries in Brown Norway and Sprague- Dawley rats. Microcirculation. 8: 45–55.
26. Gebremed hin, D., Ma, Y.H ., Falck, J.R., Roman , R.J., VanRollin s, M. an d Harde r, D.R. (1992). Mechanism of action of cerebral epoxyeicosatrienoic acids on cerebral arterial smooth muscle. Am. J. Physiol. 263: H519–H525.
27. Gebremedhin, D., Lange, A.R., Narayanan, J., Aebly, M.R., Jacobs, E.R. and Harder, D.R. (1998). Cat cerebral arterial smooth muscle cells express cytochrome P450 4A2 enzyme and produce the vasoconstrictor 20-HETE which enhances L-type Ca2+ current. J. Physiol. (Lond.) 507: 771–781. Gebremedhin, D., Lange, A.R., Lowry, T.F., Taheri, M.R., Birks, E.K., Hudetz, A.G., Narayanan, J., Falck, J.R., Okamoto, H., Roman, R.J., Nithipatikom, K., Campbell, W.B. and Harder, D.R. (2000). Production of 20-HETE and its role in autoregulation of cerebral blood flow. Circ. Res. 87: 60–65.
28. Gibson, G.G. (1989). Comparative aspects of the mammalian cytochrome P450 IV gene family. Xenobiotica 10: 1123–1148.
29. Gross, E.R., Nithipatikom, K., Hsu, A.K., Peart, J.N., Falck, J.R., Campbell, W.B. and Gross, G.J. (2004). Cytochrome P450 omega-hydroxylase inhibition reduces infarct size during reperfusion via the sarcolemmal KATP channel. J. Mol. Cell. Cardiol. 37: 1245–1249.
30. Hacein-Bey, L., Harder, D.R., Meier, H.T., Lauer, K.K. and Roman, R.J. (2004a). Improvement in angiographic vasospasm with a 20-HETE enzyme inhibitor in a subarachnoid hemorrhage dog model. In: Proceedings of the American Society of Neuroradiology, Abstract #59, American Society of Neuroradiology 42nd Meeting, Seattle, WA, p. 46.
31. Hacein-Bey, L., Roman, R.J., Lemke, D.M,, Lauer, K.K., Varelas, P.N., Torbey, M.T., Cusick, J.F. and Harder, D.R. (2004b). Evaluation of 20-hydroxy- eiscosatetraenoic acid (20-HETE) levels in normal and abno rma l bl ood and CSF. In: Proc eedings of the Ameri can Soc i ety of Neuroradiology, Abstract #66, American Society of Neuroradiology 42nd Meeting, Seattle, WA, p. 51.
32. Harder, D.R., Gebremedhin, D., Narayanan, J., Jefcoat, C., Falck, J.R., Campbell, W.B. and Roman, R.J. (1994). Formation and action of a P-450 4A metabolite of arachidonic acid in cat cerebral microvessels. Am. J. Physiol. 266: H2098–H2107.
33. Hardwick, J.P., Song, B.J., Huberman, E. and Gonzalez, F.J. (1987). Isolation, complementary DNA sequence, and regulation of rat hepatic lauric acid omega-hydroxylase (cytochrome P-450LA omega). Identification of a new cytochrome P-450 gene family. J. Biol. Chem. 262: 801–810. Hayabuchi, Y., Nakaya, Y., Matsuoka, S. and Kuroda, Y. (1998). Endothelium-derived hyperpolarizing factor activates Ca2+-activated K+ channels in porcine coronary artery smooth muscle cells. J. Cardiovasc. Pharmacol. 32: 642–649.
34. Helvig, C ., Dishman, E. and Capdevila, J.H. (1998). Molecula r, enzymatic, and regulatory characterization of rat kidney cytochromes P450 4A2 and 4A3. Biochemistry 37: 12546–12558.
35. Heng, Y.M., Kuo, C.S., Jones, P.S., Savory, R., Schulz, R.M., Tomlinson, S.R., Gray, T.J. and Bell, D.R. (1997). A novel murine P-450 gene, Cyp4a14, is part of a cluster of Cyp4a and Cyp4b, but not of CYP4F, genes in mouse and humans. Biochem. J. 325: 741–749.
36. Hercule, H.C. and Oyekan, A.O. (2000). Cytochrome P450 omega/omega-1 hydroxylase-derived eicosanoids contribute to endothelin(A) and endothelin (B) receptor-mediated vasoconstriction to endothelin-1 in the rat preglomerular arteriole. J. Pharmacol. Exp. Ther. 292: 1153–1160.
37. Hill, E. and Murphy, R.C. (1992). Quantitation of 20-hydroxy-5,8,11,14- eicosatetraenoic acid (20-HETE) produced by human polymorphonuclear leukocytes using electron capture ionization gas chromatography/mass spectrometry. Biol. Mass. Spectrom. 21: 249–253.
38. Holla, V.R., Adas, F., Imig, J.D., Zhao, X., Price, E. Jr., Olsen, N., Kovac, W.J., Magnunson, M.A., Keeney, D.S., Breyer, M.D., Falck, J.R., Waterman, M.R. and Capdevila, J.H. (2001). Alterations in the regulation of androgen-sensitive cyp 4a monooxygenase cause hypertension. Proc. Natl. Acad. Sci. U.S.A. 9: 5211–5216.
39. Honeck, H., Gross, V., Erdmann, B., Kargel, E., Neunaber, R., Milia, A.F., Schneider, W., Luft, F.C. and Schunck, W.H. (2000). Cytochrome P450-dependent renal arachidonic acid metabolism in desoxycorticosterone acetate-salt hypertensive mice. Hypertension 36: 610–616.
40. Imig, J.D., Zou, A.P., Ortiz de Montellano, P.R., Sui, Z. and Roman, R.J. (1994). Cytochrome P-450 inhibitors alter afferent arteriolar responses to elevations in pressure. Am. J. Physiol. 266: H1879–H1885.
41. Imig, J.D., Zou, A.P., Stec, D.E., Harder, D.R., Falck, J.R. and Roman, R.J. (1996). Formation and actions of 20-hydroxyeicosatetraenoic acid in rat renal arterioles. Am. J. Physiol. 270: R217–R227.
42. Imig, J.D., Pham, B.T., LeBlanc, E.A., Reddy, K.M., Falck, J.R. and Inscho, E.W. (2000). Cytochrome P450 and cyclooxygenase metabolites contribute to the endothelin-1 afferent arteriolar vasoconstrictor and calcium responses. Hypertension 35: 307–312.
43. Ishizuka, T., Ito, O., Omata, K. and Ito, S. (2004). Role of androgens in the renal production of 20- hydroxyeicosatetraenoic acid in spontaneously hypertensive rats. Nippon Jinzo Gakkai Shi 46: 685–692.
44. Ito, O., Alonso-Galicia, M., Hopp, K.A. and Roman, R.J. (1998). Localization of cytochrome P-450 4A isoforms along the rat nephron. Am. J. Physiol. 274: F395–F404.
45. Ito, O. and Roman, R.J. (1999). Role of 20-HETE in elevating chloride transport in the thick ascending limb of Dahl SS/Jr rats. Hypertension 33: 419–423.
46. Jiang, M., Mezentsev, A., Kemp, R., Byun, K., Falck, J.R., Miano, J.M., Nasjletti, A., Abraham, N.G. and Laniado-Schwartzman, M. (2004). Smooth muscle—specific expression of CYP4A1 induces endothelial sprouting in renal arterial microvessels. Circ. Res. 94: 167–174.
47. Juvela, S. (2000). Plasma endothelin concentrations after aneurysmal subarachnoid hemorrhage. J. Neurosurg. 92: 390–400.
48. Kehl, F., Cambji-Sapunar, L., Maier, K.G., Miyata, N., Kametani, S., Okamoto, H., Hudetz, A.G., Schulte, M.L., Zagorac, D., Harder, D.R. and Roman, R.J. (2002) 20-HETE contributes to the acute fall in cerebral blood flow after subarachnoid hemorrhage in the rat. Am. J. Physiol. 282: H1556– H1565.
49. Kikuta, Y., Kusunose, E., Kondo, T., Yamamoto, S., Kinoshita, H. and Kusunose, M. (1994). Cloning and expression of a novel form of leukotriene B4 omega-hydroxylase from human liver. FEBS Lett. 348: 70–74.
50. Kikuta, Y., Kasyu, H., Kusunose, E. and Kusunose, M. (2000). Expression and catalytic activity of mouse leukotriene B4 omega-hydroxylase, CYP4F14. Arch. Biochem. Biophys. 383: 225–232.
51. Kimura, S., Hanioka, N., Matsunaga, E. and Gonzalez, F.J. (1989a). The rat clofibrate-inducible CYP4A gene subfamily. I. Complete intron and exon sequence of the CYP4A1 and CYP4A2 genes, unique exon organization, and identification of a conserved 19-bp upstream element. DNA 8: 503–516.
52. Kimura, S., Hardwick, J.P., Kozak, C.A. and Gonzalez, F.J. (1989b). The rat clofibrate-inducible CYP4A subfamily. II. cDNA sequence of IVA3, mapping of the Cyp4a locus to mouse chromosome 4, and coordinate and tissue-specific regulation of the CYP4A genes. DNA 8: 517–525.
53. Lange, A., Gebremedhin, D., Narayanan, J. and Harder, D. (1997). 20-Hydroxyeicosatetraenoic acid-induced vasoconstriction and inhibition of potassium current in cerebral vascular smooth muscle is dependent on activation of protein kinase C. J. Biol. Chem. 272: 27345–27352.
54. Lasker, J.M., Chen, W.B., Wolf, I., Bloswick, B.P., Wilson, P.D. and Powell, P.K. (2000). Formation of 20-hyroxyeicosatetraenoic acid, a vasoactive and natriuretic eicosanoid, in human kidney. Role of Cyp4F2 and Cyp4A11. J. Biol. Chem. 275: 4118–4126.
55. Mathews, J.M., Dostal, L.A. and Bend, J.R. (1981). Inactivation of rabbit pulmonary cytochrome P-450 in microsomes and isolated perfusedlungs by the suicide substrate 1-aminobenzotriazole. J. Pharmacol. Exp. Ther. 235: 186–190.
56. McCarthy, E.T., Sharma, R. and Sharma, M. (2005). Protective effect of 20-hydroxyeicosatetraenoic acid (20-HETE) on glomerular protein permeability barrier. Kidney Int. 67: 152–156.
57. McGiff, J.C. and Quilley, J. (1999). 20-HETE and the kidney: resolution of old problems and new beginnings. Am. J. Physiol. 277: R607–R623.
58. Miura, H. and Gutterman, D.D. (1998). Human coronary arteriolardilation to arachidonic acid depends on cytochrome P-450 monooxygenase and Ca2+-activated K+ channels. Circ. Res. 83: 501–507.
59. Miyata, N., Taniguchi, K., Seki, T., Ishimoto, T., Sato-Watanabe, M., Yasuda, Y., Doi, M., Kametani, S., Tomishima, Y., Ueki, T., Sato, M. and Kameo, K. (2001). HET0016, a potent and selective inhibitor of 20-HETE synthesizing enzyme. Br. J. Pharmacol. 133: 325–329.
60. Miyata, N., Seki, T., Tanaka, Y., Omura, T., Taniguchi, K., Doi, M., Bandou, K., Kametani, S., Sato, M., Okuyama, S., Cambj-Sapunar, L., Harder, D.R. and Roman, R.J. (2005). Beneficial effects of a new 20-HETE synthesis inhibitor, TS-011, on hemorrhagic and ischemic stroke. J. Pharmacol. Exp. Ther. 314: 77–85.
61. Muerhoff, A.S., Williams, D.E., Reich, N.O., CaJacob, C.A., Ortiz de Montellano, P.R. and Masters, B.S. (1989). Prostaglandin and fatty acid omega- and (omega-1)-oxidation in rabbit lung. Acetylenic fatty acid mechanism-based inactivators as specific inhibitors. J. Biol. Chem. 264: 749–756.
62. Mulligan, S.J. and MacVicar, B.A. (2004). Calcium transients in astrocyte endfeet cause cerebrovascular constrictions. Nature 431: 137–138.
63. Muthalif, M.M., Benter, I.F., Karzoun, N., Fatima, S., Harper, J., Uddin,M.R. and Malik, K.U. (1998). 20-HETE mediates calcium/calmodulindependent protein kinase II-induced mitogen-activated protein kinase activation in vascular smooth muscle cells. Proc. Natl. Acad. Sci. U.S.A. 95: 12701–12706.
64. Muthalif, M.M., Benter, I.F., Khandekar, Z., Gaber, L., Estes, A., Malik, S., Parmentier, J.H., Manne, V. and Malik, K.U. (2000a). Contribution of Ras GTPase/MAP kinase and cytochrome P450 metabolites to deoxycorticosterone salt- induced hypertension. Hypertension 35: 457–463.
65. Muthalif, M.M., Karzoun, N.A., Gaber, L., Khandekar, Z., Benter, I.F., Saeed, A.E., Parmentier, J.H., Estes, A. and Malik, K.U. (2000b).Angiotensin II-induced hypertension: contribution of RasGTPase/Mitogen-activated protein kinase and cytochrome P450 metabolites. Hypertension 36: 604–609.
66. Nakagawa, K., Marji, J.S., Schwartzman, M.L., Waterman, M.R. and Capdevila, J.H. (2003). Androgen- mediated induction of the kidney arachidonate hydroxylases is associated with the development
67. of hypertension. Am. J. Physiol. 284: R1055–R1062.
68. Nakamura, M., Imaoka, S., Miura, K., Tanaka, E., Misawa, S. and Funae, Y. (1994). Induction of cytochrome P450 isozymes in rat renal microsomes by cyclosporin A. Biochem. Pharmacol. 48: 1743–1746.
69. Nakamura, M., Imaoka, S., Tanaka, E., Misawa, S. and Funae, Y. (1998). cis-Diamminedichloroplatinum induces peroxisomes as well as CYP4A1 in rat kidney. Res. Commun. Mol. Pathol. Pharmacol. 99: 23–32.
70. Nakamura, T., Sato, M., Kakinuma, H., Miyata, N., Taniguchi, K., Bando, K., Koda, A. and Kameo, K. (2003). Pyrazole and isoxazole derivatives as new, potent, and selective 20-hydroxy-5, 8, 11, 14-eicosatetraenoic acid synthase inhibitors. J. Med. Chem. 46: 5416–5427.
71. Nakamura, T., Kakinuma, H., Umemiya, H., Amada, H., Miyata, N., Taniguchi, K., Bando, K. and Sato, M. (2004a). Imidazole derivatives as new potent and selective 20-HETE synthase inhibitors. Bioorg. Med. Chem. Lett. 14: 333–336.
72. Nakamura, T., Ishii, T., Miyata, N., Taniguchi, K., Tomishima, Y., Ueki, T. and Sato, M. (2004b). Design and synthesis of 1-(4-benzoylphenyl)imidazole derivatives as new potent
20-HETE synthase inhibitors. Bioorg. Med. Chem. Lett. 14: 5305–5308.
73. Nakamura, T., Kakinuma, H., Amada, H., Miyata, N., Taniguchi, K., Koda, A. and Sato, M. (2004c). Pyrazole derivatives as new potent and selective 20-hydroxy-5,8,11,14-eicosatetraenoic acid synthase inhibitors. Bioorg. Med. Chem. 12: 6209–6219.
74. Needleman, P., Turk, J., Jakschik, B.A., Morrison, A.R. and Lefkowith, J.B. (1986). Arachidonic acid metabolism. Ann. Rev. Biochem. 55: 69–102.
75. Nithipatikom, K., DiCamelli, R.F., Kohler, S., Gumina, R.J., Falck, J.R., Campbell, W.B. and Gross, G..J. (2001). Determination of cytochrome P450 metabolites of arachidonic acid in coronary venous plasma during ischemia and reperfusion in dogs. Anal. Biochem. 292: 115–124.
76. Nithipatikom, K., Gross, E.R., Endsley, M.P., Moore, J.M., Isbell, M.A., Falck, J.R., Campbell, W.B. and Gross, G.J. (2004). Inhibition of cytochrome P450 omega-hydroxylase: a novel endogenous cardioprotective pathway. Circ. Res. 95: e65–e71.
77. Obara, K., Koide, M. and Nakayama, K. (2002). 20-Hydroxyeicosatetraenoic acid potentiates stretch-induced contraction of canine basilar artery via PKC alpha-mediated inhibition of KCa channel. Br. J. Pharmacol. 137: 1362–1370.
78. Omata, K., Abraham, N.G. and Schwartzman, M.L. (1992). Renal cytochrome P-450-arachidonic acid metabolism: localization and hormonal regulation in SHR. Am. J. Physiol. 262: F591–F599.
79. Ortiz de Montellano, P.R. and Mathews, J.M. (1981). Autocatalytic alkylation of the cytochrome P-450 prost hetihaem group by 1-a mino benzot riazole. Isolation of an NN-bridged benzyne- protoporphyrin IX adduct. Biochem. J. 195: 761–764.
80. Oyek an, A., Balazy, M. and McGiff, J.C. (1997). Renal oxygenases: differential con tribution to vasoconstriction induced by ET-1 and ANG II. Am. J. Physiol. 273: R293–R300.
81. Pickard, J.D., Walker, V., Brandt, L., Zygmunt, S. and Smythe, J. (1994). Effect of intraventricular haemorrhage and rebleeding following subarachnoid haemorrhage on CSF eicosanoids. Acta. Neurochir.(Wien). 129: 152–157.
82. Popp, R., Bau e rsachs, J., Hecker, M., F le ming , I. and Bu sse, R. (1996). A transferable, beta-naphthoflavone-inducible, hyperpolarizing factor is synthesized by native and cultured porcine coronary endothelial cells. J. Physiol. (Lond.) 497: 699–709.
83. Powell, P.K., Wolf, I., Jin, R. and Lasker, J.M. (1998). Metabolism of arachidonic acid to 20-hydroxy-5, 8, 11, 14-eicosatetraenoic acid by P450 enzymes in human liver: involvement of CYP4F2 and CYP4A11. J. Pharmacol. Exp. Ther. 285: 1327–1336.
84. Pratt, P.F., Falck, J.R., Reddy, K.M., Kurian, J.B. and Campbell, W.B. (1998). 20-HETE relaxes bovine coronary arteries through the release of prostacyclin. Hypertension 31: 237–241.
85. Quigley, R., Baum, M., Reddy, K.M., Griener. J.C. and Falck, J.R. (2000). Effects of 20-HETE and 19(S)-
86. HETE on rabbit proximal straight tubule volume transport. Am. J. Physiol. 278: F949–F953.
87. Quilley J., Qiu, Y. and Hirt, J. (2003). Inhibitors of 20-hydroxyeicosatetraenoic acid reduce renal vasoconstrictor responsiveness. J. Pharmacol. Exp. Ther. 307: 223–229.
88. Randriamboavonjy, V., Busse, R. and Fleming, I. (2003). 20-HETE-induced contraction of small coronary arteries depends on the activation of Rho-kinase. Hypertension 41: 801–806.
89. Randriamboavonjy, V., Kiss, L., Falck, J.R., Busse, R. and Fleming, I. (2005). The synthesis of 20-HETE in small porcine coronary arteries antagonizes EDHF-mediated relaxation. Cardiovasc. Res. 65: 487–494.
90. Reckelhoff, J.F. (2001). Gender differences in the regulation of blood pressure. Hypertension 37: 1199–1208.
91. Roman, R.J. (2002). P-450 metabolites of arachidonic acid in the control of cardiovascular function. Physiol. Rev. 82: 131–185.
92. Rosolowsky, M., Falck, J.R. and Campbell, W.B. (1996). Metabolism of arachidonic acid by canine polymorphonuclear leukocytes synthesis of lipoxygenase and omega-oxidized metabolites. Biochim. Biophys. Acta. 1300: 143–150.
93. Sacerdoti, D., Borsato, M., Rigotti, P., Amodio, P., Angeli, P., Ferraresso, M., Plebani, M. and Gatta, A. (1991). Increased renal production of cytochrome P450-dependent metabolites of arachidonic acid in cyclosporine-induced nephrotoxicity. Adv. Prostaglandin Thromboxane Leukot. Res. 21B: 689–692.
94. Sacerdoti, D., Balazy, M., Angeli, P., Gatta, A. and McGiff, J.C. (1997). Eicosanoid excretion in hepatic cirrhosis. Predominance of 20-HETE. J. Clin. Invest. 100: 1264–1270.
95. Saida, A., Ito, H., Shibuya, T. and Watanabe, Y. (1997). Time-course alterations of monoamine levels and cerebral blood flow in brain regions after subarachnoid hemorrhage in rats. Brain Res. Bull. 43: 69–80.
96. Sato, M., Ishii, T., Kobayashi-Matsunaga, Y., Amada, H., Taniguchi, K., Miyata, N. and Kameo, K. (2001). Discovery of a N’-hydroxyphenylformamidine derivative HET0016 as a potent and selective 20- HETE synthase inhibitor. Bioorg. Med. Chem. Lett. 11: 2993–2995.
97. Schwartzman, M., Ferreri, N.R., Carroll, M.A., Songu-Mize , E. and McGiff, J.C. (1985). Renal cytochrome P450-related arachidonate metabolite inhibits (Na+- K+)-ATPase. Nature 314: 620–622.
98. Seifert, V., Loffler, B.M., Zimmermann, M., Roux, S. and Stolke, D. (1995). Endothelin concentrations in patients with aneurysmal subarachnoid hemorrhage. Correlation with cerebral vasospasm, delayed ischemic neurological deficits, and volume of hematoma. J. Neurosurg. 82: 55–62.
99. Seki, T., Ishimoto, T., Sakurai, T., Yasuda, Y., Taniguchi, K., Doi, M., Sato, M., Roman, R.J. and Miyata, N. (200 5). Increased excretion of urinary 20- HETE in rats with cyclosporine-induced nephrotoxicity. J. Pharmacol. Sci. 97: 132–137.
100. Simpson, A.E. (1997). The cytochrome P450 4 (CYP4) family. Gen. Pharmacol. 28: 351–359.
101. Su, P., Kaushal, K.M. and Kroetz, D.L. (1998). Inhibition of renal arachidonic acid omega-hydroxylase activity with ABT reduces blood pressure in the SHR. Am. J. Physiol. 275: R426–R438.
102. Sun, C.W., Alonso-Galicia, M., Taheri, M.R., Falck, J.R., Harder, D.R. and Roman, R.J. (1998). Nitric oxide-20-hydroxyeicosatetraenoic acid interaction in the regulation ofK+ channel activity and vascular tone in renal arterioles. Circ. Res. 83: 1069–1079.
103. Sun, C.W., Falck, J.R., Harder, D.R. and Roman, R.J. (1999). Role of tyrosine kinase and PKC in the vasoconstrictor response to 20-HETE in renal arterioles. Hypertension 33: 414–418.
104. Sun, C.W., Falck, J.R., Okamoto, H., Harder, D.R. and Roman, R.J. (2000). Role of cGMP versus 20- HETE in the vasodilator response to nitric oxide in rat cerebral arteries. Am. J. Physiol. 279: H339–H350.
105. Wang, M.H., Brand-Schieber, E., Zand, B.A., Nguyen, X., Falck, J.R., Balu, N. and Schwartzman, M.L. (1998). Cytochrome P 450 -d er ived arachidon ic a c id metabolism in the rat kidney characterization of selective inhibitors. J. Pharmacol. Exp. Ther. 284: 966–973
106. Wang, M. H., Zand, B. A., Nasjletti, A. and Laniado-Schwartzman, M. (200 2). Renal 20- hydroxyeicosatetraenoic acid synthesis during pregnancy. Am. J. Physiol. 282: R383–R389.
107. Wang, M.H., Wang, J., Chang, H.H., Zand, B.A., Jiang, M., Nasjletti, A. and Laniado-Schwartzman, M. (2003). Regulation of renal CYP4A expression and 20-HETE synthesis by nitric oxide in pregnant rats. Am. J. Physiol. 285: F295–F302.
108. Ward, N.C., Rivera, J., Hodgson, J., Puddey, I.B., Beilin, L.J., Falck, J.R. and Croft, K.D. (2004). Urinary 20-hydroxyeicosatetraenoic acid is associated with endothelial dysfunction in humans. Circulation 110: 438–443.
109. Ward, N.C., Puddey , I. B., Hodgson, J.M., Beilin, L.J. and Croft, K . D. (2005). Urinary 20- hydroxyeicosatetraenoic acid excretion is associated with oxidative stress in hypertensive subjects. Free Radic. Biol. Med. 38: 1032–1106.
110. Watzer, B., Reinalter, S., Seyberth, H.W. and Schweer, H. (2000). Determination of free and glucuronide conjugated 20-hydroxyarachidonic acid (20-HETE) in urine by gas chromatography/negative ion chemical ionization mass spectrometry.Prostaglandins Leukot. Essent. Fatty Acids 62: 175–181.
111. Xu, F., Straub, W.O., Pa, W., Su, P., Maier, K.G., Yu, M., Roman, R.J., Ortiz de Montellano, P.R. and Kroetz, D.L. (2002). Antihypertensive effect of mechanism-based inhibition of renal arachidonic acid -hydroxylase activity. Am. J. Physiol. 283: R710–R720.
112. Yu, M., Alonso-Galicia, M., Sun, C.W., Roman, R.J., Ono, N., Hirano, H., Ishimoto, T., Reddy, Y.K., Katipally , K.R., Redd y, K.M., Gopal, V.R., Yu, J., Takhi, M. and Falck , J.R. (2 003) . 20- hydroxyeicosatetraenoic acid (20-HETE): structural determinants for renal vasoconstriction. Bioorg. Med. Chem. 11: 2803–2821.
113. Yu, M., Cambj-Sapunar, L., Kehl, F., Maier, K.G., Takeuchi, K., Miyata, N., Ishimoto, T., Reddy, L.M., Falck, J.R., Gebremedhin, D., Harder, D.R. and Roman, R.J. (2004). Effects of a 20-HETE antagonist and agonists on cerebral vascular tone. Eur. J. Pharmacol. 486: 297–306.
114. Zhou, Y., Lin, S., Chang, H.H., Du, J., Dong, Z., Dorrance, A.M., Brands, M.W. and Wang, M.H. (2005). Gender differences of renal CYP-derived eicosanoid synthesis in rats fed a high-fat diet. Am. J. Hypertension 18: 530–537.
115. Zou, A.P., Ma, Y.H., Sui, Z.H., Ortiz de Montellano, P.R., Clark, J.E., Masters, B.S. and Roman, R.J. (1994). Effects of 17-octadecynoic acid, a suicide-substrate inhibitor of cytochrome P450 fatty acid omega-hydroxylase, on renal function in rats. J. Pharmacol. Exp. Ther. 268: 474–481.
116. Zou, A.P., Fleming, J.T., Falck, J.R., Jacobs, E.R., Gebremedhin, D., Harder, D.R. and Roman, R.J. (1996). Stereospecific effects of epoxyeicosatrienoic acids on renal vascular tone and K+ -channel activity. Am. J. Physiol. 270: F822–F832.
2. Amaral SL, Maier KG, Schippers DN, Roman RJ, Greene AS: CYP4A metabolites of arachidonic acid and VEGF are mediators of skeletal muscle angiogenesis. Am J Physiol Heart Circ Physiol 2003;284:H1528-1535.
3. Kaduce TL, Fang X, Harmon SD, Oltman CL, Dellsperger KC, Teesch LM, Gopal VR, Falck JR, Campbell WB, Weintraub NL, Spector AA: 20-hydroxyeicosatetraenoic acid (20-HETE) metabolism in coronary endothelial cells. J Biol Chem 2004;279:2648-2656.
4. Randriamboavonjy V, Kiss L, Falck JR, Busse R, Fleming I: The synthesis of 20-HETE in small porcine coronary arteries antagonizes EDHF-mediated relaxation. Cardiovasc Res 2005;65:487-494.
5. Omata K, Abraham NG, Schwartzman ML: Renal cytochrome P-450-arachidonic acid metabolism: localization and hormonal regulation in SHR. Am J Physiol 1992;262:F591-599.
6. Oyekan AO, McGiff JC: Functional response of the rat kidney to inhibition of nitric oxide synthesis: role of cytochrome p450-derived arachidonate metabolites. Br J Pharmacol 1998;125:1065-1073.
7. Wang MH, Wang J, Chang HH, Zand BA, Jiang M, Nasjletti A, Laniado-Schwartzman M: Regulation of renal CYP4A expression and 20-HETE synthesis by nitric oxide in pregnant rats. Am J Physiol Renal Physiol 2003;285:F295-302.
8. Sarkis A, Lopez B, Roman RJ: Role of 20-hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids in hypertension. Curr Opin Nephrol Hypertens 2004;13:205-214.
9. Harder DR, Gebremedhin D, Narayanan J, Jefcoat C, Falck JR,Campbell WB, Roman R: Formation and action of a P-450 4A metabolite of arachidonic acid in cat cerebral microvessels. Am J Physiol 1994;266:H2098-2107.
10. Yu M, Cambj-Sapunar L, Kehl F, Maier KG, Takeuchi K, Miyata N, Ishimoto T, Reddy LM, Falck JR, Gebremedhin D, Harder DR, Roman RJ: Effects of a 20-HETE antagonist and agonists on cerebral vascular tone. Eur J Pharmacol 2004;486:297-306.
11. Miyata N, Seki T, Tanaka Y, Omura T, Taniguchi K, Doi M, Bandou K, Kametani S, Sato M, Okuyama S, Cambj-Sapunar L, Harder DR, Roman RJ: Beneficial effects of a new 20-hydroxyeicosatetraenoic acid synthesis inhibitor, TS-011 [N-(3-chloro-4-morpholin-4-yl) phenyl-N'-hydroxyimido formamide], on hemorrhagic and ischemic stroke. J Pharmacol Exp Ther 2005;314:77-85.
12. Takeuchi K, Miyata N, Renic M, Harder DR, Roman RJ: Hemoglobin, NO, and 20-HETE interactions in mediating cerebral vasoconstriction following SAH. Am J Physiol Regul Integr Comp Physiol 2006;290:R84-89.
13. Gainer JV, Bellamine A, Dawson EP, Womble KE, Grant SW, Wang Y, Cupples LA, Guo CY, Demissie S, O'Donnell CJ, Brown NJ, Waterman MR, Capdevila JH: Functional variant of CYP4A11 20-hydroxyeicosatetraenoic acid synthase is associated with essential hypertension. Circulation 2005;111:63-69.
14. Fleming I: Cytochrome P-450 under pressure: more evidence for a link between 20-hydroxyeicosatetraenoic acid and hypertension. Circulation 2005;111:5-7.
15. Cho BH, Park BL, Kim LH, Chung HS, Shin HD: Highly polymorphic human CYP4A11 gene. J Hum Genet 2005;50:259-263.
16. Xu F, Falck JR, Ortiz de Montellano PR, Kroetz DL: Catalytic activity and isoform-specific inhibition of rat cytochrome p450 4F enzymes. J Pharmacol Exp Ther 2004;308:887-895.
17. Parker TA, Grover TR, Kinsella JP, Falck JR, Abman SH: Inhibition of 20-HETE abolishes the myogenic response during NOS antagonism in the ovine fetal pulmonary circulation. Am J Physiol Lung Cell Mol Physiol 2005;289:L261-267.
18. Yu M, Alonso-Galicia M, Sun CW, Roman RJ, Ono N, Hirano H, Ishimoto T, Reddy YK, Katipally KR, Reddy KM, Gopal VR, Yu J, Takhi M, Falck JR: 20-hydroxyeicosatetraenoic acid (20-HETE): structural determinants for renal vasoconstriction. Bioorg Med Chem 2003;11:2803-2821.
19. Quilley J, Qiu Y, Hirt J: Inhibitors of 20-hydroxyeicosatetraenoic acid reduce renal vasoconstrictor responsiveness. J Pharmacol Exp Ther 2003;307:223-229.
20. Bellamine A, Wang Y, Waterman MR, Gainer JV, 3rd, Dawson EP, Brown NJ, Capdevila JH: Characterization of the CYP4A11 gene, a second CYP4A gene in humans. Arch Biochem Biophys 2003;409:221-227.
21. Kikuta Y, Kusunose E, Kusunose M: Prostaglandin and leukotriene omega-hydroxylases. Prostaglandins Other Lipid Mediat 2002;68-69:345-362.
22. Alonso-Galicia M, Maier KG, Greene AS, Cowley AW, Jr., Roman RJ: Role of 20-hydroxyeicosatetraenoic acid in the renal and vasoconstrictor actions of angiotensin II. Am J Physiol Regul Integr Comp Physiol 2002;283:R60-68.
23. Roman RJ, Maier KG, Sun CW, Harder DR, Alonso-Galicia M: Renal and cardiovascular actions of 20-hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids. Clin Exp Pharmacol Physiol 2000;27:855-865.
24. Lasker JM, Chen WB, Wolf I, Bloswick BP, Wilson PD, Powell PK: Formation of 20-hydroxyeicosatetraenoic acid, a vasoactive and natriuretic eicosanoid, in human kidney. Role of Cyp4F2 and Cyp4A11. J Biol Chem 2000;275:4118-4126.
25. Kikuta Y, Kusunose E, Kusunose M: Characterization of human liver leukotriene B(4) omega-hydroxylase P450 (CYP4F2). J Biochem (Tokyo) 2000;127:1047-1052.
26. Kawashima H, Naganuma T, Kusunose E, Kono T, Yasumoto R, Sugimura K, Kishimoto T: Human fatty acid omega-hydroxylase, CYP4A11: determination of complete genomic sequence and characterization of purified recombinant protein. Arch Biochem Biophys 2000;378:333-339.
27. Hoch U, Zhang Z, Kroetz DL, Ortiz de Montellano PR: Structural determination of the substrate specificities and regioselectivities of the rat and human fatty acid omega-hydroxylases. Arch Biochem Biophys 2000;373:63-71.
28. Kikuta Y, Miyauchi Y, Kusunose E, Kusunose M: Expression and molecular cloning of human liver leukotriene B4 omega-hydroxylase (CYP4F2) gene. DNA Cell Biol 1999;18:723-730.
29. Chang YT, Loew GH: Homology modeling and substrate binding study of human CYP4A11 enzyme. Proteins 1999;34:403-415.
30. Powell PK, Wolf I, Jin R, Lasker JM: Metabolism of arachidonic acid to 20-hydroxy-5,8,11, 14-eicosatetraenoic acid by P450 enzymes in human liver: involvement of CYP4F2 and CYP4A11. J Pharmacol Exp Ther 1998;285:1327-1336.
31. Crespi CL, Chang TK, Waxman DJ: Determination of CYP4A11-catalyzed lauric acid 12-hydroxylation by high-performance liquid chromatography with radiometric detection. Methods Mol Biol 1998;107:163-167.
32. Ma YH, Gebremedhin D, Schwartzman ML, Falck JR, Clark JE, Masters BS, Harder DR, Roman RJ: 20-Hydroxyeicosatetraenoic acid is an endogenous vasoconstrictor of canine renal arcuate arteries. Circ Res 1993;72:126-136.
33. Imaoka S, Ogawa H, Kimura S, Gonzalez FJ: Complete cDNA sequence and cDNA-directed expression of CYP4A11, a fatty acid omega-hydroxylase expressed in human kidney. DNA Cell Biol 1993;12:893-899.
1. Alonso-Galicia, M., Sun, C.W., Falck, J.R., Harder, D.R. and Roman, R.J. (1998). Contribution of 20-HETE to the vasodilator actions of nitric oxide in renal arteries. Am. J. Physiol. 275: F370–F378.
2. Alonso-Galicia, M., Falck, J.R., Reddy, K.M. and Roman, R.J. (1999). 20-HETE agonists and antagonists in the renal circulation. Am. J. Physiol. 277: F790–F796.
3. Alonso-Galicia, M., Maier, K.G., Greene, A.S., Cowley, A.W. Jr. and Roman, R.J. (2002). Role of 20- hydroxyeicosatetraenoic acid in the renal and vasoconstrictor actions of angiotensin II. Am. J. Physiol. 283: R60–R68.
4. Amaral, S.L., Maier, K.G., Schippers, D.N., Roman, R.J. and Greene,A.S. (2003). CYP4A metabolites of arachidonic acid and VEGF are mediators of skeletal muscle angiogenesis. Am. J. Physiol. 284: H1528–H1535.
5. Bednar, M.M., Gross, C.E., Balazy, M.K., Belosludtsev, Y., Colella, D.T., Falck, J.R. and Balazy, M. (2000). 16(R)-hydroxy-5, 8, 11, 14- eicosatetraenoic acid, a new arachidonate metabolite in human polymorphonuclear leukocytes. Biochem. Pharmacol. 60: 447–455.
6. Christmas, P., Jones, J.P., Patten, C.J., Rock, D.A., Zheng, Y., Cheng, S.M., Weber, B.M., Carlesso, N., Scadden, D.T., Rettie, A.E. and Soberman, R.J. (2001). Alternative splicing determines the function of CYP4F3 by switching substrate specificity. J. Biol. Chem. 276: 38166–38172.
7. Cambj-Sapunar, L., Yu, M., Harder, D.R. and Roman, R.J. (2003). Contribution of 5-hydroxytryptamine1B receptors and 20-hydroxyeiscosatetraenoic acid to fall in cerebral blood flow after subarachnoid hemorrhage. Stroke 34: 1269–1275.
8. Campbe ll, W. B. , Gebr eme d hin, D., Pratt, P. F. and Harde r , D.R. ( 1996) . Id entif i cation of epoxyeicosatrienoic acids as endothelium-derived hyperpolarizing factors. Circ. Res. 78: 415–425
9. Capdevila, J., Chacos, N., Werringloer, J., Prough, R.A. and Estabrook, R.W. (1981). Liver microsomal cytochrome P-450 and the oxidative metabolism of arachidonic acid. Proc. Natl. Acad. Sci. U.S.A. 78: 5362–5366.
10. Carroll, M.A., Sala, A., Dunn, C.E., McGiff, J.C. and Murphy, R.C. (1991). Structural identification of cytochrome P450-dependent arachidonate metabolites formed by rabbit medullary thick ascending limb cells. J. Biol. Chem. 266: 12306–12312.
11. Carroll, M.A., Balazy, M., Margiotta, P., Huang, D.D., Falck, J.R. and McGiff, J.C. (1996). Cytochrome P-450-dependent HETEs: profile of biological activity and stimulation by vasoactive peptides. Am. J. Physiol. 271: R863–R869.
12. Carroll, M.A., Balazy, M., Huang, D.D., Rybalova, S., Falck, J.R. and McGiff, J.C. (1997). Cytochrome P450-derived renal HETEs: storage and release. Kidney Int. 51: 1696–1702.
13. Chen, P., Guo, M., Wygle, D., Edwards, P.A., Falck, J.R., Roman, R.J. and Scicli, A.G. (2005). Inhibitors of cytochrome P450 4A suppress angiogenic responses. Am. J. Pathol. 166: 615–624.
14. Christmas, P., Jones, J.P., Patten, C.J., Rock, D.A., Zheng, Y., Cheng, S.M., Weber, B.M., Carlesso, N., Scadden, D.T., Rettie, A.E. and Soberman, R.J. (2001). Alternative splicing determines the function of CYP4F3 by switching substrate specificity. J. Biol. Chem. 276: 38166–38172.
15. Croft, K.D., McGiff, J.C., Sanchez-Mendoza, A. and Carroll, M.A. (2000). Angiotensin II releases 20- HETE from rat renal microvessels. Am. J. Physiol. 279: F544–F551.
16. Cui, X., Kawashima, H., Barclay, T.B., Peters, J.M., Gonzalez, F.J., Morgan, E.T. and Strobel, H.W. (2001). Molecular cloning and regulation of expression of two novel mouse CYP4F genes: ex pressi on i n pero xi so me pro l ifera t o r -a ct iv at ed rec e pt or a l p h a - defi ci ent m i c e upo n lipopolysaccharide and clofibrate challenges. J. Pharmacol. Exp. Ther. 296: 542–550.
17. Dahly-Vernon, A.J., Sharma, M., McCarthy, E.T., Savin, V.J., Ledbetter, S.R. and Roman, R.J. (2005). Transforming growth factor-beta, 20-HETE interaction, and glomerular injury in Dahl salt- sensitive rats. Hypertension 45: 643–648.
18. Eckman, D.M., Hopkins, N., McBride, C. and Keef, K.D. (1998). Endothelium-dependent relaxation and hyperpolarization in guinea-pig coronary artery: role of epoxyeicosatrienoic acid. Br. J. Pharmacol. 124: 181–189.
19. Escalante, B., Erlij, D., Falck, J.R. and McGiff, J.C. (1991). Effect of cytochrome P450 arachidonate metabolites on ion transport in rabbit kidney loop of Henle. Science 251: 799–802.
20. Escalante, B., Erlij, D., Falck, J.R. and McGiff, J.C. (1994).Cytochrome P-450 arachidonate metabolites affect ion fluxes in rabbit medullary thick ascending limb. Am. J. Physiol. 266: C1775–C1782.
21. Fisslthaler, B., Popp, R., Kiss, L., Potente, M., Harder, D.R., Fleming, I. and Busse, R. (1999). Cytochrome P450 2C is an EDHF synthase in coronary arteries. Nature 401: 493–497.
22. Fleming, I. (2001). Cytochrome p450 and vascular homeostasis. Circ. Res. 89: 753–762.
23. Fleming, I., Michaelis, U.R., Bredenkotter, D., Fisslthaler, B., Dehghani, F., Brandes, R.P. and Busse, R. (2001). Endothelium-derived hyperpolarizing factor synthase (Cytochrome P450 2C9) is a functionally significant source of reactive oxygen species in coronary arteries. Circ. Res. 88: 44–51.
24. Frisbee, J.C., Roman, R.J., Krishna, U.M., Falck, J.R. and Lombard, J.H. (2001a). 20-HETE modulates myogenic response of skeletal muscle resistance arteries from hypertensive Dahl-SS rats. Am. J. Physiol. 280: H1066–H1074.
25. Frisbee, J.C., Roman, R.J., Falck, J.R., Krishna, U.M. and Lombard, J.H. (2001b). 20-HETE contributes to myogenic activation of skeletal muscle resistance arteries in Brown Norway and Sprague- Dawley rats. Microcirculation. 8: 45–55.
26. Gebremed hin, D., Ma, Y.H ., Falck, J.R., Roman , R.J., VanRollin s, M. an d Harde r, D.R. (1992). Mechanism of action of cerebral epoxyeicosatrienoic acids on cerebral arterial smooth muscle. Am. J. Physiol. 263: H519–H525.
27. Gebremedhin, D., Lange, A.R., Narayanan, J., Aebly, M.R., Jacobs, E.R. and Harder, D.R. (1998). Cat cerebral arterial smooth muscle cells express cytochrome P450 4A2 enzyme and produce the vasoconstrictor 20-HETE which enhances L-type Ca2+ current. J. Physiol. (Lond.) 507: 771–781. Gebremedhin, D., Lange, A.R., Lowry, T.F., Taheri, M.R., Birks, E.K., Hudetz, A.G., Narayanan, J., Falck, J.R., Okamoto, H., Roman, R.J., Nithipatikom, K., Campbell, W.B. and Harder, D.R. (2000). Production of 20-HETE and its role in autoregulation of cerebral blood flow. Circ. Res. 87: 60–65.
28. Gibson, G.G. (1989). Comparative aspects of the mammalian cytochrome P450 IV gene family. Xenobiotica 10: 1123–1148.
29. Gross, E.R., Nithipatikom, K., Hsu, A.K., Peart, J.N., Falck, J.R., Campbell, W.B. and Gross, G.J. (2004). Cytochrome P450 omega-hydroxylase inhibition reduces infarct size during reperfusion via the sarcolemmal KATP channel. J. Mol. Cell. Cardiol. 37: 1245–1249.
30. Hacein-Bey, L., Harder, D.R., Meier, H.T., Lauer, K.K. and Roman, R.J. (2004a). Improvement in angiographic vasospasm with a 20-HETE enzyme inhibitor in a subarachnoid hemorrhage dog model. In: Proceedings of the American Society of Neuroradiology, Abstract #59, American Society of Neuroradiology 42nd Meeting, Seattle, WA, p. 46.
31. Hacein-Bey, L., Roman, R.J., Lemke, D.M,, Lauer, K.K., Varelas, P.N., Torbey, M.T., Cusick, J.F. and Harder, D.R. (2004b). Evaluation of 20-hydroxy- eiscosatetraenoic acid (20-HETE) levels in normal and abno rma l bl ood and CSF. In: Proc eedings of the Ameri can Soc i ety of Neuroradiology, Abstract #66, American Society of Neuroradiology 42nd Meeting, Seattle, WA, p. 51.
32. Harder, D.R., Gebremedhin, D., Narayanan, J., Jefcoat, C., Falck, J.R., Campbell, W.B. and Roman, R.J. (1994). Formation and action of a P-450 4A metabolite of arachidonic acid in cat cerebral microvessels. Am. J. Physiol. 266: H2098–H2107.
33. Hardwick, J.P., Song, B.J., Huberman, E. and Gonzalez, F.J. (1987). Isolation, complementary DNA sequence, and regulation of rat hepatic lauric acid omega-hydroxylase (cytochrome P-450LA omega). Identification of a new cytochrome P-450 gene family. J. Biol. Chem. 262: 801–810. Hayabuchi, Y., Nakaya, Y., Matsuoka, S. and Kuroda, Y. (1998). Endothelium-derived hyperpolarizing factor activates Ca2+-activated K+ channels in porcine coronary artery smooth muscle cells. J. Cardiovasc. Pharmacol. 32: 642–649.
34. Helvig, C ., Dishman, E. and Capdevila, J.H. (1998). Molecula r, enzymatic, and regulatory characterization of rat kidney cytochromes P450 4A2 and 4A3. Biochemistry 37: 12546–12558.
35. Heng, Y.M., Kuo, C.S., Jones, P.S., Savory, R., Schulz, R.M., Tomlinson, S.R., Gray, T.J. and Bell, D.R. (1997). A novel murine P-450 gene, Cyp4a14, is part of a cluster of Cyp4a and Cyp4b, but not of CYP4F, genes in mouse and humans. Biochem. J. 325: 741–749.
36. Hercule, H.C. and Oyekan, A.O. (2000). Cytochrome P450 omega/omega-1 hydroxylase-derived eicosanoids contribute to endothelin(A) and endothelin (B) receptor-mediated vasoconstriction to endothelin-1 in the rat preglomerular arteriole. J. Pharmacol. Exp. Ther. 292: 1153–1160.
37. Hill, E. and Murphy, R.C. (1992). Quantitation of 20-hydroxy-5,8,11,14- eicosatetraenoic acid (20-HETE) produced by human polymorphonuclear leukocytes using electron capture ionization gas chromatography/mass spectrometry. Biol. Mass. Spectrom. 21: 249–253.
38. Holla, V.R., Adas, F., Imig, J.D., Zhao, X., Price, E. Jr., Olsen, N., Kovac, W.J., Magnunson, M.A., Keeney, D.S., Breyer, M.D., Falck, J.R., Waterman, M.R. and Capdevila, J.H. (2001). Alterations in the regulation of androgen-sensitive cyp 4a monooxygenase cause hypertension. Proc. Natl. Acad. Sci. U.S.A. 9: 5211–5216.
39. Honeck, H., Gross, V., Erdmann, B., Kargel, E., Neunaber, R., Milia, A.F., Schneider, W., Luft, F.C. and Schunck, W.H. (2000). Cytochrome P450-dependent renal arachidonic acid metabolism in desoxycorticosterone acetate-salt hypertensive mice. Hypertension 36: 610–616.
40. Imig, J.D., Zou, A.P., Ortiz de Montellano, P.R., Sui, Z. and Roman, R.J. (1994). Cytochrome P-450 inhibitors alter afferent arteriolar responses to elevations in pressure. Am. J. Physiol. 266: H1879–H1885.
41. Imig, J.D., Zou, A.P., Stec, D.E., Harder, D.R., Falck, J.R. and Roman, R.J. (1996). Formation and actions of 20-hydroxyeicosatetraenoic acid in rat renal arterioles. Am. J. Physiol. 270: R217–R227.
42. Imig, J.D., Pham, B.T., LeBlanc, E.A., Reddy, K.M., Falck, J.R. and Inscho, E.W. (2000). Cytochrome P450 and cyclooxygenase metabolites contribute to the endothelin-1 afferent arteriolar vasoconstrictor and calcium responses. Hypertension 35: 307–312.
43. Ishizuka, T., Ito, O., Omata, K. and Ito, S. (2004). Role of androgens in the renal production of 20- hydroxyeicosatetraenoic acid in spontaneously hypertensive rats. Nippon Jinzo Gakkai Shi 46: 685–692.
44. Ito, O., Alonso-Galicia, M., Hopp, K.A. and Roman, R.J. (1998). Localization of cytochrome P-450 4A isoforms along the rat nephron. Am. J. Physiol. 274: F395–F404.
45. Ito, O. and Roman, R.J. (1999). Role of 20-HETE in elevating chloride transport in the thick ascending limb of Dahl SS/Jr rats. Hypertension 33: 419–423.
46. Jiang, M., Mezentsev, A., Kemp, R., Byun, K., Falck, J.R., Miano, J.M., Nasjletti, A., Abraham, N.G. and Laniado-Schwartzman, M. (2004). Smooth muscle—specific expression of CYP4A1 induces endothelial sprouting in renal arterial microvessels. Circ. Res. 94: 167–174.
47. Juvela, S. (2000). Plasma endothelin concentrations after aneurysmal subarachnoid hemorrhage. J. Neurosurg. 92: 390–400.
48. Kehl, F., Cambji-Sapunar, L., Maier, K.G., Miyata, N., Kametani, S., Okamoto, H., Hudetz, A.G., Schulte, M.L., Zagorac, D., Harder, D.R. and Roman, R.J. (2002) 20-HETE contributes to the acute fall in cerebral blood flow after subarachnoid hemorrhage in the rat. Am. J. Physiol. 282: H1556– H1565.
49. Kikuta, Y., Kusunose, E., Kondo, T., Yamamoto, S., Kinoshita, H. and Kusunose, M. (1994). Cloning and expression of a novel form of leukotriene B4 omega-hydroxylase from human liver. FEBS Lett. 348: 70–74.
50. Kikuta, Y., Kasyu, H., Kusunose, E. and Kusunose, M. (2000). Expression and catalytic activity of mouse leukotriene B4 omega-hydroxylase, CYP4F14. Arch. Biochem. Biophys. 383: 225–232.
51. Kimura, S., Hanioka, N., Matsunaga, E. and Gonzalez, F.J. (1989a). The rat clofibrate-inducible CYP4A gene subfamily. I. Complete intron and exon sequence of the CYP4A1 and CYP4A2 genes, unique exon organization, and identification of a conserved 19-bp upstream element. DNA 8: 503–516.
52. Kimura, S., Hardwick, J.P., Kozak, C.A. and Gonzalez, F.J. (1989b). The rat clofibrate-inducible CYP4A subfamily. II. cDNA sequence of IVA3, mapping of the Cyp4a locus to mouse chromosome 4, and coordinate and tissue-specific regulation of the CYP4A genes. DNA 8: 517–525.
53. Lange, A., Gebremedhin, D., Narayanan, J. and Harder, D. (1997). 20-Hydroxyeicosatetraenoic acid-induced vasoconstriction and inhibition of potassium current in cerebral vascular smooth muscle is dependent on activation of protein kinase C. J. Biol. Chem. 272: 27345–27352.
54. Lasker, J.M., Chen, W.B., Wolf, I., Bloswick, B.P., Wilson, P.D. and Powell, P.K. (2000). Formation of 20-hyroxyeicosatetraenoic acid, a vasoactive and natriuretic eicosanoid, in human kidney. Role of Cyp4F2 and Cyp4A11. J. Biol. Chem. 275: 4118–4126.
55. Mathews, J.M., Dostal, L.A. and Bend, J.R. (1981). Inactivation of rabbit pulmonary cytochrome P-450 in microsomes and isolated perfusedlungs by the suicide substrate 1-aminobenzotriazole. J. Pharmacol. Exp. Ther. 235: 186–190.
56. McCarthy, E.T., Sharma, R. and Sharma, M. (2005). Protective effect of 20-hydroxyeicosatetraenoic acid (20-HETE) on glomerular protein permeability barrier. Kidney Int. 67: 152–156.
57. McGiff, J.C. and Quilley, J. (1999). 20-HETE and the kidney: resolution of old problems and new beginnings. Am. J. Physiol. 277: R607–R623.
58. Miura, H. and Gutterman, D.D. (1998). Human coronary arteriolardilation to arachidonic acid depends on cytochrome P-450 monooxygenase and Ca2+-activated K+ channels. Circ. Res. 83: 501–507.
59. Miyata, N., Taniguchi, K., Seki, T., Ishimoto, T., Sato-Watanabe, M., Yasuda, Y., Doi, M., Kametani, S., Tomishima, Y., Ueki, T., Sato, M. and Kameo, K. (2001). HET0016, a potent and selective inhibitor of 20-HETE synthesizing enzyme. Br. J. Pharmacol. 133: 325–329.
60. Miyata, N., Seki, T., Tanaka, Y., Omura, T., Taniguchi, K., Doi, M., Bandou, K., Kametani, S., Sato, M., Okuyama, S., Cambj-Sapunar, L., Harder, D.R. and Roman, R.J. (2005). Beneficial effects of a new 20-HETE synthesis inhibitor, TS-011, on hemorrhagic and ischemic stroke. J. Pharmacol. Exp. Ther. 314: 77–85.
61. Muerhoff, A.S., Williams, D.E., Reich, N.O., CaJacob, C.A., Ortiz de Montellano, P.R. and Masters, B.S. (1989). Prostaglandin and fatty acid omega- and (omega-1)-oxidation in rabbit lung. Acetylenic fatty acid mechanism-based inactivators as specific inhibitors. J. Biol. Chem. 264: 749–756.
62. Mulligan, S.J. and MacVicar, B.A. (2004). Calcium transients in astrocyte endfeet cause cerebrovascular constrictions. Nature 431: 137–138.
63. Muthalif, M.M., Benter, I.F., Karzoun, N., Fatima, S., Harper, J., Uddin,M.R. and Malik, K.U. (1998). 20-HETE mediates calcium/calmodulindependent protein kinase II-induced mitogen-activated protein kinase activation in vascular smooth muscle cells. Proc. Natl. Acad. Sci. U.S.A. 95: 12701–12706.
64. Muthalif, M.M., Benter, I.F., Khandekar, Z., Gaber, L., Estes, A., Malik, S., Parmentier, J.H., Manne, V. and Malik, K.U. (2000a). Contribution of Ras GTPase/MAP kinase and cytochrome P450 metabolites to deoxycorticosterone salt- induced hypertension. Hypertension 35: 457–463.
65. Muthalif, M.M., Karzoun, N.A., Gaber, L., Khandekar, Z., Benter, I.F., Saeed, A.E., Parmentier, J.H., Estes, A. and Malik, K.U. (2000b).Angiotensin II-induced hypertension: contribution of RasGTPase/Mitogen-activated protein kinase and cytochrome P450 metabolites. Hypertension 36: 604–609.
66. Nakagawa, K., Marji, J.S., Schwartzman, M.L., Waterman, M.R. and Capdevila, J.H. (2003). Androgen- mediated induction of the kidney arachidonate hydroxylases is associated with the development
67. of hypertension. Am. J. Physiol. 284: R1055–R1062.
68. Nakamura, M., Imaoka, S., Miura, K., Tanaka, E., Misawa, S. and Funae, Y. (1994). Induction of cytochrome P450 isozymes in rat renal microsomes by cyclosporin A. Biochem. Pharmacol. 48: 1743–1746.
69. Nakamura, M., Imaoka, S., Tanaka, E., Misawa, S. and Funae, Y. (1998). cis-Diamminedichloroplatinum induces peroxisomes as well as CYP4A1 in rat kidney. Res. Commun. Mol. Pathol. Pharmacol. 99: 23–32.
70. Nakamura, T., Sato, M., Kakinuma, H., Miyata, N., Taniguchi, K., Bando, K., Koda, A. and Kameo, K. (2003). Pyrazole and isoxazole derivatives as new, potent, and selective 20-hydroxy-5, 8, 11, 14-eicosatetraenoic acid synthase inhibitors. J. Med. Chem. 46: 5416–5427.
71. Nakamura, T., Kakinuma, H., Umemiya, H., Amada, H., Miyata, N., Taniguchi, K., Bando, K. and Sato, M. (2004a). Imidazole derivatives as new potent and selective 20-HETE synthase inhibitors. Bioorg. Med. Chem. Lett. 14: 333–336.
72. Nakamura, T., Ishii, T., Miyata, N., Taniguchi, K., Tomishima, Y., Ueki, T. and Sato, M. (2004b). Design and synthesis of 1-(4-benzoylphenyl)imidazole derivatives as new potent
20-HETE synthase inhibitors. Bioorg. Med. Chem. Lett. 14: 5305–5308.
73. Nakamura, T., Kakinuma, H., Amada, H., Miyata, N., Taniguchi, K., Koda, A. and Sato, M. (2004c). Pyrazole derivatives as new potent and selective 20-hydroxy-5,8,11,14-eicosatetraenoic acid synthase inhibitors. Bioorg. Med. Chem. 12: 6209–6219.
74. Needleman, P., Turk, J., Jakschik, B.A., Morrison, A.R. and Lefkowith, J.B. (1986). Arachidonic acid metabolism. Ann. Rev. Biochem. 55: 69–102.
75. Nithipatikom, K., DiCamelli, R.F., Kohler, S., Gumina, R.J., Falck, J.R., Campbell, W.B. and Gross, G..J. (2001). Determination of cytochrome P450 metabolites of arachidonic acid in coronary venous plasma during ischemia and reperfusion in dogs. Anal. Biochem. 292: 115–124.
76. Nithipatikom, K., Gross, E.R., Endsley, M.P., Moore, J.M., Isbell, M.A., Falck, J.R., Campbell, W.B. and Gross, G.J. (2004). Inhibition of cytochrome P450 omega-hydroxylase: a novel endogenous cardioprotective pathway. Circ. Res. 95: e65–e71.
77. Obara, K., Koide, M. and Nakayama, K. (2002). 20-Hydroxyeicosatetraenoic acid potentiates stretch-induced contraction of canine basilar artery via PKC alpha-mediated inhibition of KCa channel. Br. J. Pharmacol. 137: 1362–1370.
78. Omata, K., Abraham, N.G. and Schwartzman, M.L. (1992). Renal cytochrome P-450-arachidonic acid metabolism: localization and hormonal regulation in SHR. Am. J. Physiol. 262: F591–F599.
79. Ortiz de Montellano, P.R. and Mathews, J.M. (1981). Autocatalytic alkylation of the cytochrome P-450 prost hetihaem group by 1-a mino benzot riazole. Isolation of an NN-bridged benzyne- protoporphyrin IX adduct. Biochem. J. 195: 761–764.
80. Oyek an, A., Balazy, M. and McGiff, J.C. (1997). Renal oxygenases: differential con tribution to vasoconstriction induced by ET-1 and ANG II. Am. J. Physiol. 273: R293–R300.
81. Pickard, J.D., Walker, V., Brandt, L., Zygmunt, S. and Smythe, J. (1994). Effect of intraventricular haemorrhage and rebleeding following subarachnoid haemorrhage on CSF eicosanoids. Acta. Neurochir.(Wien). 129: 152–157.
82. Popp, R., Bau e rsachs, J., Hecker, M., F le ming , I. and Bu sse, R. (1996). A transferable, beta-naphthoflavone-inducible, hyperpolarizing factor is synthesized by native and cultured porcine coronary endothelial cells. J. Physiol. (Lond.) 497: 699–709.
83. Powell, P.K., Wolf, I., Jin, R. and Lasker, J.M. (1998). Metabolism of arachidonic acid to 20-hydroxy-5, 8, 11, 14-eicosatetraenoic acid by P450 enzymes in human liver: involvement of CYP4F2 and CYP4A11. J. Pharmacol. Exp. Ther. 285: 1327–1336.
84. Pratt, P.F., Falck, J.R., Reddy, K.M., Kurian, J.B. and Campbell, W.B. (1998). 20-HETE relaxes bovine coronary arteries through the release of prostacyclin. Hypertension 31: 237–241.
85. Quigley, R., Baum, M., Reddy, K.M., Griener. J.C. and Falck, J.R. (2000). Effects of 20-HETE and 19(S)-
86. HETE on rabbit proximal straight tubule volume transport. Am. J. Physiol. 278: F949–F953.
87. Quilley J., Qiu, Y. and Hirt, J. (2003). Inhibitors of 20-hydroxyeicosatetraenoic acid reduce renal vasoconstrictor responsiveness. J. Pharmacol. Exp. Ther. 307: 223–229.
88. Randriamboavonjy, V., Busse, R. and Fleming, I. (2003). 20-HETE-induced contraction of small coronary arteries depends on the activation of Rho-kinase. Hypertension 41: 801–806.
89. Randriamboavonjy, V., Kiss, L., Falck, J.R., Busse, R. and Fleming, I. (2005). The synthesis of 20-HETE in small porcine coronary arteries antagonizes EDHF-mediated relaxation. Cardiovasc. Res. 65: 487–494.
90. Reckelhoff, J.F. (2001). Gender differences in the regulation of blood pressure. Hypertension 37: 1199–1208.
91. Roman, R.J. (2002). P-450 metabolites of arachidonic acid in the control of cardiovascular function. Physiol. Rev. 82: 131–185.
92. Rosolowsky, M., Falck, J.R. and Campbell, W.B. (1996). Metabolism of arachidonic acid by canine polymorphonuclear leukocytes synthesis of lipoxygenase and omega-oxidized metabolites. Biochim. Biophys. Acta. 1300: 143–150.
93. Sacerdoti, D., Borsato, M., Rigotti, P., Amodio, P., Angeli, P., Ferraresso, M., Plebani, M. and Gatta, A. (1991). Increased renal production of cytochrome P450-dependent metabolites of arachidonic acid in cyclosporine-induced nephrotoxicity. Adv. Prostaglandin Thromboxane Leukot. Res. 21B: 689–692.
94. Sacerdoti, D., Balazy, M., Angeli, P., Gatta, A. and McGiff, J.C. (1997). Eicosanoid excretion in hepatic cirrhosis. Predominance of 20-HETE. J. Clin. Invest. 100: 1264–1270.
95. Saida, A., Ito, H., Shibuya, T. and Watanabe, Y. (1997). Time-course alterations of monoamine levels and cerebral blood flow in brain regions after subarachnoid hemorrhage in rats. Brain Res. Bull. 43: 69–80.
96. Sato, M., Ishii, T., Kobayashi-Matsunaga, Y., Amada, H., Taniguchi, K., Miyata, N. and Kameo, K. (2001). Discovery of a N’-hydroxyphenylformamidine derivative HET0016 as a potent and selective 20- HETE synthase inhibitor. Bioorg. Med. Chem. Lett. 11: 2993–2995.
97. Schwartzman, M., Ferreri, N.R., Carroll, M.A., Songu-Mize , E. and McGiff, J.C. (1985). Renal cytochrome P450-related arachidonate metabolite inhibits (Na+- K+)-ATPase. Nature 314: 620–622.
98. Seifert, V., Loffler, B.M., Zimmermann, M., Roux, S. and Stolke, D. (1995). Endothelin concentrations in patients with aneurysmal subarachnoid hemorrhage. Correlation with cerebral vasospasm, delayed ischemic neurological deficits, and volume of hematoma. J. Neurosurg. 82: 55–62.
99. Seki, T., Ishimoto, T., Sakurai, T., Yasuda, Y., Taniguchi, K., Doi, M., Sato, M., Roman, R.J. and Miyata, N. (200 5). Increased excretion of urinary 20- HETE in rats with cyclosporine-induced nephrotoxicity. J. Pharmacol. Sci. 97: 132–137.
100. Simpson, A.E. (1997). The cytochrome P450 4 (CYP4) family. Gen. Pharmacol. 28: 351–359.
101. Su, P., Kaushal, K.M. and Kroetz, D.L. (1998). Inhibition of renal arachidonic acid omega-hydroxylase activity with ABT reduces blood pressure in the SHR. Am. J. Physiol. 275: R426–R438.
102. Sun, C.W., Alonso-Galicia, M., Taheri, M.R., Falck, J.R., Harder, D.R. and Roman, R.J. (1998). Nitric oxide-20-hydroxyeicosatetraenoic acid interaction in the regulation ofK+ channel activity and vascular tone in renal arterioles. Circ. Res. 83: 1069–1079.
103. Sun, C.W., Falck, J.R., Harder, D.R. and Roman, R.J. (1999). Role of tyrosine kinase and PKC in the vasoconstrictor response to 20-HETE in renal arterioles. Hypertension 33: 414–418.
104. Sun, C.W., Falck, J.R., Okamoto, H., Harder, D.R. and Roman, R.J. (2000). Role of cGMP versus 20- HETE in the vasodilator response to nitric oxide in rat cerebral arteries. Am. J. Physiol. 279: H339–H350.
105. Wang, M.H., Brand-Schieber, E., Zand, B.A., Nguyen, X., Falck, J.R., Balu, N. and Schwartzman, M.L. (1998). Cytochrome P 450 -d er ived arachidon ic a c id metabolism in the rat kidney characterization of selective inhibitors. J. Pharmacol. Exp. Ther. 284: 966–973
106. Wang, M. H., Zand, B. A., Nasjletti, A. and Laniado-Schwartzman, M. (200 2). Renal 20- hydroxyeicosatetraenoic acid synthesis during pregnancy. Am. J. Physiol. 282: R383–R389.
107. Wang, M.H., Wang, J., Chang, H.H., Zand, B.A., Jiang, M., Nasjletti, A. and Laniado-Schwartzman, M. (2003). Regulation of renal CYP4A expression and 20-HETE synthesis by nitric oxide in pregnant rats. Am. J. Physiol. 285: F295–F302.
108. Ward, N.C., Rivera, J., Hodgson, J., Puddey, I.B., Beilin, L.J., Falck, J.R. and Croft, K.D. (2004). Urinary 20-hydroxyeicosatetraenoic acid is associated with endothelial dysfunction in humans. Circulation 110: 438–443.
109. Ward, N.C., Puddey , I. B., Hodgson, J.M., Beilin, L.J. and Croft, K . D. (2005). Urinary 20- hydroxyeicosatetraenoic acid excretion is associated with oxidative stress in hypertensive subjects. Free Radic. Biol. Med. 38: 1032–1106.
110. Watzer, B., Reinalter, S., Seyberth, H.W. and Schweer, H. (2000). Determination of free and glucuronide conjugated 20-hydroxyarachidonic acid (20-HETE) in urine by gas chromatography/negative ion chemical ionization mass spectrometry.Prostaglandins Leukot. Essent. Fatty Acids 62: 175–181.
111. Xu, F., Straub, W.O., Pa, W., Su, P., Maier, K.G., Yu, M., Roman, R.J., Ortiz de Montellano, P.R. and Kroetz, D.L. (2002). Antihypertensive effect of mechanism-based inhibition of renal arachidonic acid -hydroxylase activity. Am. J. Physiol. 283: R710–R720.
112. Yu, M., Alonso-Galicia, M., Sun, C.W., Roman, R.J., Ono, N., Hirano, H., Ishimoto, T., Reddy, Y.K., Katipally , K.R., Redd y, K.M., Gopal, V.R., Yu, J., Takhi, M. and Falck , J.R. (2 003) . 20- hydroxyeicosatetraenoic acid (20-HETE): structural determinants for renal vasoconstriction. Bioorg. Med. Chem. 11: 2803–2821.
113. Yu, M., Cambj-Sapunar, L., Kehl, F., Maier, K.G., Takeuchi, K., Miyata, N., Ishimoto, T., Reddy, L.M., Falck, J.R., Gebremedhin, D., Harder, D.R. and Roman, R.J. (2004). Effects of a 20-HETE antagonist and agonists on cerebral vascular tone. Eur. J. Pharmacol. 486: 297–306.
114. Zhou, Y., Lin, S., Chang, H.H., Du, J., Dong, Z., Dorrance, A.M., Brands, M.W. and Wang, M.H. (2005). Gender differences of renal CYP-derived eicosanoid synthesis in rats fed a high-fat diet. Am. J. Hypertension 18: 530–537.
115. Zou, A.P., Ma, Y.H., Sui, Z.H., Ortiz de Montellano, P.R., Clark, J.E., Masters, B.S. and Roman, R.J. (1994). Effects of 17-octadecynoic acid, a suicide-substrate inhibitor of cytochrome P450 fatty acid omega-hydroxylase, on renal function in rats. J. Pharmacol. Exp. Ther. 268: 474–481.
116. Zou, A.P., Fleming, J.T., Falck, J.R., Jacobs, E.R., Gebremedhin, D., Harder, D.R. and Roman, R.J. (1996). Stereospecific effects of epoxyeicosatrienoic acids on renal vascular tone and K+ -channel activity. Am. J. Physiol. 270: F822–F832.
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