Epoxyeicosatrienoic acids, hypertension, and kidney injury

Hypertension

Volumn 65, Issue 3, 2015, Pages 476-482

  Imig, John D ^a  

^a MEDICAL COLLEGE OF WISCONSIN   (United States)

Author keywords

chronic renal insufficiency; eicosanoids; hypertension; kidney

Indexed keywords

ANTIHYPERTENSIVE AGENT; DOCOSAHEXAENOIC ACID; EPOXIDE HYDROLASE; EPOXYICOSATRIENOIC ACID; FISH OIL; ICOSAPENTAENOIC ACID; OMEGA 3 FATTY ACID; 11,12-EPOXY-5,8,14-EICOSATRIENOIC ACID; 14,15-EPOXY-5,8,11-EICOSATRIENOIC ACID; DIHOMO GAMMA LINOLENIC ACID; FATTY ACID;

ARTICLE; CLINICAL TRIAL (TOPIC); CONTROLLED CLINICAL TRIAL (TOPIC); DIET THERAPY; ENDOTHELIAL DYSFUNCTION; HUMAN; HYPERTENSION; INFLAMMATION; KIDNEY DISEASE; KIDNEY INJURY; LINSEED; PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM; VASCULAR ENDOTHELIAL DYSFUNCTION; ANALOGS AND DERIVATIVES; ANIMAL; DISEASE COURSE; DISEASE MODEL; KIDNEY DISEASES; METABOLISM; MOUSE; PATHOPHYSIOLOGY; PHYSIOLOGY; RAT; VASCULAR ENDOTHELIUM;

8,11,14-EICOSATRIENOIC ACID; ANIMALS; ANTIHYPERTENSIVE AGENTS; DISEASE MODELS, ANIMAL; DISEASE PROGRESSION; ENDOTHELIUM, VASCULAR; FATTY ACIDS; HUMANS; HYPERTENSION; KIDNEY DISEASES; MICE; RATS;

EID: 84924237583     PISSN: 0194911X     EISSN: 15244563     Source Type: Journal    
DOI: 10.1161/HYPERTENSIONAHA.114.03585     Document Type: Article

References (80)

1. Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P, Van Lente F, Levey AS. Prevalence of chronic kidney disease in the United States. JAMA. 2007;298:2038-2047. doi: 10.1001/jama.298.17.2038.
2. Foley RN, Collins AJ. End-stage renal disease in the United States: an update from the United States Renal Data System. J Am Soc Nephrol. 2007;18:2644-2648. doi: 10.1681/ASN.2007020220.
3. American Heart Association. High blood pressure statistics. http://www.americanheart.org/presenter.jhtml?identifier=4621. Accessed August 2014.
4. Crook ED. The role of hypertension, obesity, and diabetes in causing renal vascular disease. Am J Med. Sci. 1999;317:183-188.
5. Barri YM. Hypertension and kidney disease: a deadly connection. Curr Hypertens Rep. 2008;10:39-45.
6. Muntner P, Davis BR, Cushman WC, Bangalore S, Calhoun DA, Pressel SL, Black HR, Kostis JB, Probstfield JL, Whelton PK, Rahman M; ALLHAT Collaborative Research Group. Treatment-resistant hypertension and the incidence of cardiovascular disease and end-stage renal disease: results from the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). Hypertension. 2014;64:1012-1021. doi: 10.1161/HYPERTENSIONAHA.114.03850.
7. Imig JD. Epoxides and soluble epoxide hydrolase in cardiovascular physiology. Physiol Rev. 2012;92:101-130. doi: 10.1152/physrev.00021.2011.
8. Capdevila J, Wang W. Role of cytochrome P450 epoxygenase in regulating renal membrane transport and hypertension. Curr Opin Nephrol Hypertens. 2013;22:163-169. doi: 10.1097/MNH.0b013e32835d911e.
9. Campbell WB, Gebremedhin D, Pratt PF, Harder DR. Identification of epoxyeicosatrienoic acids as endothelium-derived hyperpolarizing factors. Circ Res. 1996;78:415-423.
10. Fisslthaler B, Popp R, Kiss L, Potente M, Harder DR, Fleming I, Busse R. Cytochrome P450 2C is an EDHF synthase in coronary arteries. Nature. 1999;401:493-497. doi: 10.1038/46816.
11. Capdevila JH, Pidkovka N, Mei S, Gong Y, Falck JR, Imig JD, Harris RC, Wang W. The Cyp2c44 epoxygenase regulates epithelial sodium channel activity and the blood pressure responses to increased dietary salt. J Biol Chem. 2014;289:4377-4386. doi: 10.1074/jbc.M113.508416.
12. Node K, Huo Y, Ruan X, Yang B, Spiecker M, Ley K, Zeldin DC, Liao JK. Anti-inflammatory properties of cytochrome P450 epoxygenase-derived eicosanoids. Science. 1999;285:1276-1279.
13. Makita K, Takahashi K, Karara A, Jacobson HR, Falck JR, Capdevila JH. Experimental and/or genetically controlled alterations of the renal microsomal cytochrome P450 epoxygenase induce hypertension in rats fed a high salt diet. J Clin Invest. 1994;94:2414-2420. doi: 10.1172/JCI117608.
14. Zhao X, Pollock DM, Inscho EW, Zeldin DC, Imig JD. Decreased renal cytochrome P450 2C enzymes and impaired vasodilation are associated with angiotensin salt-sensitive hypertension. Hypertension. 2003;41(3 pt 2):709-714. doi: 10.1161/01.HYP.0000047877.36743.FA.
15. Imig JD, Zhao X, Capdevila JH, Morisseau C, Hammock BD. Soluble epoxide hydrolase inhibition lowers arterial blood pressure in angiotensin II hypertension. Hypertension. 2002;39(2 pt 2):690-694.
16. Messer-Létienne I, Bernard N, Roman RJ, Sassard J, Benzoni D. Cytochrome P-450 arachidonate metabolite inhibition improves renal function in Lyon hypertensive rats. Am J Hypertens. 1999;12(4 pt 1):398-404.
17. Kaergel E, Muller DN, Honeck H, Theuer J, Shagdarsuren E, Mullally A, Luft FC, Schunck WH. P450-dependent arachidonic acid metabolism and angiotensin II-induced renal damage. Hypertension. 2002;40:273-279.
18. Zhao X, Yamamoto T, Newman JW, Kim IH, Watanabe T, Hammock BD, Stewart J, Pollock JS, Pollock DM, Imig JD. Soluble epoxide hydrolase inhibition protects the kidney from hypertension-induced damage. J Am Soc Nephrol. 2004;15:1244-1253.
19. Karara A, Makita K, Jacobson HR, Falck JR, Guengerich FP, DuBois RN, Capdevila JH. Molecular cloning, expression, and enzymatic characterization of the rat kidney cytochrome P-450 arachidonic acid epoxygenase. J Biol Chem. 1993;268:13565-13570.
20. Sun P, Antoun J, Lin DH, Yue P, Gotlinger KH, Capdevila J, Wang WH. Cyp2c44 epoxygenase is essential for preventing the renal sodium absorption during increasing dietary potassium intake. Hypertension. 2012;59:339-347. doi: 10.1161/HYPERTENSIONAHA.111.178475.
21. Lee CR, Imig JD, Edin ML, et al. Endothelial expression of human cytochrome P450 epoxygenases lowers blood pressure and attenuates hyper-tension-induced renal injury in mice. FASEB J. 2010;24:3770-3781. doi: 10.1096/fj.10-160119.
22. Khan MA, Pavlov TS, Christian SV, Neckar J, Staruschenko A, Gauthier KM, Capdevila JH, Falck JR, Campbell WB, Imig JD. Epoxyeicosatrienoic acid (EET) analog lowers blood pressure through vasodilation and sodium channel inhibition. Clin Sci. 2014;127:463-474.
23. Nakagawa K, Holla VR, Wei Y, et al. Salt-sensitive hypertension is associated with dysfunctional Cyp4a10 gene and kidney epithelial sodium channel. J Clin Invest. 2006;116:1696-1702. doi: 10.1172/JCI27546.
24. Sun P, Liu W, Lin DH, Yue P, Kemp R, Satlin LM, Wang WH. Epoxyeicosatrienoic acid activates BK channels in the cortical collecting duct. J Am Soc Nephrol. 2009;20:513-523. doi: 10.1681/ASN.2008040427.
25. Sun P, Lin DH, Yue P, Jiang H, Gotlinger KH, Schwartzman ML, Falck JR, Goli M, Wang WH. High potassium intake enhances the inhibitory effect of 11,12-EET on ENaC. J Am Soc Nephrol. 2010;21:1667-1677. doi: 10.1681/ASN.2009111110.
26. Fleming I. DiscrEET regulators of homeostasis: epoxyeicosatrienoic acids, cytochrome P450 epoxygenases and vascular inflammation. Trends Pharmacol Sci. 2007;28:448-452. doi: 10.1016/j.tips.2007.08.002.
27. Imig JD, Inscho EW, Deichmann PC, Reddy KM, Falck JR. Afferent arteriolar vasodilation to the sulfonimide analog of 11, 12-epoxyeicosatrienoic acid involves protein kinase A. Hypertension. 1999;33(1 pt 2):408-413.
28. Imig JD, Dimitropoulou C, Reddy DS, White RE, Falck JR. Afferent arteriolar dilation to 11, 12-EET analogs involves PP2A activity and Ca2+-activated K+ Channels. Microcirculation. 2008;15:137-150. doi: 10.1080/10739680701456960.
29. Zhao X, Dey A, Romanko OP, Stepp DW, Wang MH, Zhou Y, Jin L, Pollock JS, Webb RC, Imig JD. Decreased epoxygenase and increased epoxide hydrolase expression in the mesenteric artery of obese Zucker rats. Am J Physiol Regul Integr Comp Physiol. 2005;288:R188-R196. doi: 10.1152/ajpregu.00018.2004.
30. Bellien J, Joannides R. Epoxyeicosatrienoic acid pathway in human health and diseases. J Cardiovasc Pharmacol. 2013;61:188-196. doi: 10.1097/FJC.0b013e318273b007.
31. Yang T, Peng R, Guo Y, Shen L, Zhao S, Xu D. The role of 14,15-dihydroxyeicosatrienoic acid levels in inflammation and its relationship to lipoproteins. Lipids Health Dis. 2013;12:151. doi: 10.1186/1476-511X-12-151.
32. Bellien J, Remy-Jouet I, Iacob M, Blot E, Mercier A, Lucas D, Dreano Y, Gutierrez L, Donnadieu N, Thuillez C, Joannides R. Impaired role of epoxyeicosatrienoic acids in the regulation of basal conduit artery diameter during essential hypertension. Hypertension. 2012;60:1415-1421. doi: 10.1161/HYPERTENSIONAHA.112.201087.
33. Fischer R, Konkel A, Mehling H, Blossey K, Gapelyuk A, Wessel N, von Schacky C, Dechend R, Muller DN, Rothe M, Luft FC, Weylandt K, Schunck WH. Dietary omega-3 fatty acids modulate the eicosanoid profile in man primarily via the CYP-epoxygenase pathway. J Lipid Res. 2014;55:1150-1164. doi: 10.1194/jlr.M047357.
34. Larsen BT, Gutterman DD, Sato A, Toyama K, Campbell WB, Zeldin DC, Manthati VL, Falck JR, Miura H. Hydrogen peroxide inhibits cytochrome p450 epoxygenases: interaction between two endotheliumderived hyperpolarizing factors. Circ Res. 2008;102:59-67. doi: 10.1161/CIRCRESAHA.107.159129.
35. Larsen BT, Miura H, Hatoum OA, Campbell WB, Hammock BD, Zeldin DC, Falck JR, Gutterman DD. Epoxyeicosatrienoic and dihydroxyeicosatrienoic acids dilate human coronary arterioles via BK(Ca) channels: implications for soluble epoxide hydrolase inhibition. Am J Physiol Heart Circ Physiol. 290: H491-H499, 2006.
36. Zhang J, Patel MB, Griffiths R, Mao A, Song YS, Karlovich NS, Sparks MA, Jin H, Wu M, Lin EE, Crowley SD. Tumor necrosis factor-α produced in the kidney contributes to angiotensin II-dependent hypertension. Hypertension. 2014;64:1275-1281. doi: 10.1161/HYPERTENSIONAHA.114.03863.
37. Rudemiller N, Lund H, Jacob HJ, Geurts AM, Mattson DL; PhysGen Knockout Program. CD247 modulates blood pressure by altering T-lymphocyte infiltration in the kidney. Hypertension. 2014;63:559-564. doi: 10.1161/HYPERTENSIONAHA.113.02191.
38. Harrison DG, Guzik TJ, Lob HE, Madhur MS, Marvar PJ, Thabet SR, Vinh A, Weyand CM. Inflammation, immunity, and hypertension. Hypertension. 2011;57:132-140. doi: 10.1161/HYPERTENSIONAHA.110.163576.
39. Manhiani M, Quigley JE, Knight SF, Tasoobshirazi S, Moore T, Brands MW, Hammock BD, Imig JD. Soluble epoxide hydrolase gene deletion attenuates renal injury and inflammation with DOCA-salt hypertension. Am J Physiol Renal Physiol. 2009;297:F740-F748. doi: 10.1152/ajprenal.00098.2009.
40. Deng Y, Edin ML, Theken KN, Schuck RN, Flake GP, Kannon MA, DeGraff LM, Lih FB, Foley J, Bradbury JA, Graves JP, Tomer KB, Falck JR, Zeldin DC, Lee CR. Endothelial CYP epoxygenase overexpression and soluble epoxide hydrolase disruption attenuate acute vascular inflammatory responses in mice. FASEB J. 2011;25:703-713. doi: 10.1096/fj.10-171488.
41. Spiecker M, Darius H, Hankeln T, Soufi M, Sattler AM, Schaefer JR, Node K, Börgel J, Mügge A, Lindpaintner K, Huesing A, Maisch B, Zeldin DC, Liao JK. Risk of coronary artery disease associated with polymorphism of the cytochrome P450 epoxygenase CYP2J2. Circulation. 2004;110:2132-2136. doi: 10.1161/01.CIR.0000143832.91812.60.
42. Dreisbach AW, Japa S, Sigel A, Parenti MB, Hess AE, Srinouanprachanh SL, Rettie AE, Kim H, Farin FM, Hamm LL, Lertora JJ. The Prevalence of CYP2C8, 2C9, 2J2, and soluble epoxide hydrolase polymorphisms in African Americans with hypertension. Am J Hypertens. 2005;18:1276-1281. doi: 10.1016/j.amjhyper.2005.04.019.
43. Yu BN, Luo CH, Wang D, Wang A, Li Z, Zhang W, Mo W, Zhou HH. CYP2C9 allele variants in Chinese hypertension patients and healthy controls. Clin Chim Acta. 2004;348:57-61. doi: 10.1016/j.cccn.2004.04.028.
44. Polonikov AV, Ivanov VP, Solodilova MA, Khoroshaya IV, Kozhuhov MA, Ivakin VE, Katargina LN, Kolesnikova OE. A common polymorphism G-50T in cytochrome P450 2J2 gene is associated with increased risk of essential hypertension in a Russian population. Dis Markers. 2008;24:119-126.
45. King LM, Gainer JV, David GL, Dai D, Goldstein JA, Brown NJ, Zeldin DC. Single nucleotide polymorphisms in the CYP2J2 and CYP2C8 genes and the risk of hypertension. Pharmacogenet Genomics. 2005;15:7-13.
46. Lee CR, Pretorius M, Schuck RN, Burch LH, Bartlett J, Williams SM, Zeldin DC, Brown NJ. Genetic variation in soluble epoxide hydrolase (EPHX2) is associated with forearm vasodilator responses in humans. Hypertension. 2011;57:116-122. doi: 10.1161/HYPERTENSIONAHA.110.161695.
47. Bellien J, Iacob M, Gutierrez L, Isabelle M, Lahary A, Thuillez C, Joannides R. Crucial role of NO and endothelium-derived hyperpolarizing factor in human sustained conduit artery flow-mediated dilatation. Hypertension. 2006;48:1088-1094. doi: 10.1161/01.HYP.0000246672.72188.bd.
48. Bellien J, Iacob M, Remy-Jouet I, Lucas D, Monteil C, Gutierrez L, Vendeville C, Dreano Y, Mercier A, Thuillez C, Joannides R. Epoxyeicosatrienoic acids contribute with altered nitric oxide and endo-thelin-1 pathways to conduit artery endothelial dysfunction in essential hypertension. Circulation. 2012;125:1266-1275. doi: 10.1161/CIRCULATIONAHA.111.070680.
49. Imig JD, Hammock BD. Soluble epoxide hydrolase as a therapeutic target for cardiovascular diseases. Nat Rev Drug Discov. 2009;8:794-805. doi: 10.1038/nrd2875.
50. Imig JD. Targeting epoxides for organ damage in hypertension. J Cardiovasc Pharmacol. 2010;56:329-335. doi: 10.1097/FJC.0b013e3181e96e0c.
51. A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Doses of GSK2256294 in Healthy Volunteers, and Single and Repeat Doses of GSK2256294 in Adult Male Moderately Obese Smokers. http://clinicaltrials.gov/ct2/show/NCT01762774?term=epoxide+hydrolase&rank=2.
52. Marino JP, Jr. Soluble epoxide hydrolase, a target with multiple opportunities for cardiovascular drug discovery. Curr Top Med Chem. 2009;9:452-463.
53. Caligiuri SP, Aukema HM, Ravandi A, Guzman R, Dibrov E, Pierce GN. Flaxseed consumption reduces blood pressure in patients with hypertension by altering circulating oxylipins via an α-linolenic acid-induced inhibition of soluble epoxide hydrolase. Hypertension. 2014;64:53-59. doi: 10.1161/HYPERTENSIONAHA.114.03179.
54. Kim J, Imig JD, Yang J, Hammock BD, Padanilam BJ. Inhibition of soluble epoxide hydrolase prevents renal interstitial fibrosis and inflammation. Am J Physiol Renal Physiol. 2014;307:F971-F980. doi: 10.1152/ajprenal.00256.2014.
55. Ulu A, Harris TR, Morisseau C, Miyabe C, Inoue H, Schuster G, Dong H, Iosif AM, Liu JY, Weiss RH, Chiamvimonvat N, Imig JD, Hammock BD. Anti-inflammatory effects of ω-3 polyunsaturated fatty acids and soluble epoxide hydrolase inhibitors in angiotensin-II-dependent hypertension. J Cardiovasc Pharmacol. 2013;62:285-297. doi: 10.1097/FJC.0b013e318298e460.
56. Westphal C, Konkel A, Schunck WH. CYP-eicosanoids-a new link between omega-3 fatty acids and cardiac disease? Prostaglandins Other Lipid Mediat. 2011;96:99-108. doi: 10.1016/j.prostaglandins.2011.09.001.
57. Falck JR, Wallukat G, Puli N, Goli M, Arnold C, Konkel A, Rothe M, Fischer R, Müller DN, Schunck WH. 17®, 18(S)-epoxyeicosatetraenoic acid, a potent eicosapentaenoic acid (EPA) derived regulator of cardiomyocyte contraction: structure-activity relationships and stable analogues. J Med Chem. 2011;54:4109-4118. doi: 10.1021/jm200132q.
58. Sudhahar V, Shaw S, Imig JD. Epoxyeicosatrienoic acid analogs and vascular function. Curr Med Chem. 2010;17:1181-1190.
59. Falck JR, Koduru SR, Mohapatra S, Manne R, Atcha R, Manthati VL, Capdevila JH, Christian S, Imig JD, Campbell WB. 14,15-Epoxyeicosa-5,8,11-trienoic Acid (14,15-EET) surrogates: carboxylate modifications. J Med Chem. 2014;57:6965-6972. doi: 10.1021/jm500262m.
60. Imig JD, Elmarakby A, Nithipatikom K, Wei S, Capdevila JH, Tuniki VR, Sangras B, Anjaiah S, Manthati VL, Sudarshan Reddy D, Falck JR. Development of epoxyeicosatrienoic acid analogs with in vivo anti-hypertensive actions. Front Physiol. 2010;1:157. doi: 10.3389/fphys.2010.00157.
61. Sodhi K, Inoue K, Gotlinger KH, Canestraro M, Vanella L, Kim DH, Manthati VL, Koduru SR, Falck JR, Schwartzman ML, Abraham NG. Epoxyeicosatrienoic acid agonist rescues the metabolic syndrome phenotype of HO-2-null mice. J Pharmacol Exp Ther. 2009;331:906-916. doi: 10.1124/jpet.109.157545.
62. Batchu SN, Lee SB, Qadhi RS, Chaudhary KR, El-Sikhry H, Kodela R, Falck JR, Seubert JM. Cardioprotective effect of a dual acting epoxyeicosatrienoic acid analogue towards ischaemia reperfusion injury. Br J Pharmacol. 2011;162:897-907. doi: 10.1111/j.1476-5381.2010.01093.x.
63. Khan MA, Liu J, Kumar G, Skapek SX, Falck JR, Imig JD. Novel orally active epoxyeicosatrienoic acid (EET) analogs attenuate cisplatin nephrotoxicity. FASEB J. 2013;27:2946-2956. doi: 10.1096/fj.12-218040.
64. Khan MAH, Manthati V, Errabelli R, Pavlov TS, Staruschenko A, Falck JR, Imig JD. An orally active epoxyeicosatrienoic acid analog attenuates kidney injury in hypertensive Dahl salt sensitive rat. Hypertension. 2013;62:905-913.
65. Panigrahy D, Edin ML, Lee CR, et al. Epoxyeicosanoids stimulate multiorgan metastasis and tumor dormancy escape in mice. J Clin Invest. 2012;122:178-191. doi: 10.1172/JCI58128.
66. Pozzi A, Popescu V, Yang S, Mei S, Shi M, Puolitaival SM, Caprioli RM, Capdevila JH. The anti-tumorigenic properties of peroxisomal proliferator-activated receptor alpha are arachidonic acid epoxygenasemediated. J Biol Chem. 2010;285:12840-12850. doi: 10.1074/jbc.M109.081554.
67. Zhang W, Li H, Dong H, Liao J, Hammock BD, Yang GY. Soluble epoxide hydrolase deficiency inhibits dextran sulfate sodium-induced colitis and carcinogenesis in mice. Anticancer Res. 2013;33:5261-5271.
68. Zhang W, Liao J, Li H, Dong H, Bai H, Yang A, Hammock BD, Yang GY. Reduction of inflammatory bowel disease-induced tumor development in IL-10 knockout mice with soluble epoxide hydrolase gene deficiency. Mol Carcinog. 2013;52:726-738. doi: 10.1002/mc.21918.
69. Zhang G, Panigrahy D, Hwang SH, Yang J, Mahakian LM, Wettersten HI, Liu JY, Wang Y, Ingham ES, Tam S, Kieran MW, Weiss RH, Ferrara KW, Hammock BD. Dual inhibition of cyclooxygenase-2 and soluble epoxide hydrolase synergistically suppresses primary tumor growth and metastasis. Proc Natl Acad Sci U S A. 2014;111:11127-11132. doi: 10.1073/pnas.1410432111.
70. Gupta NC, Davis CM, Nelson JW, Young JM, Alkayed NJ. Soluble epoxide hydrolase: sex differences and role in endothelial cell survival. Arterioscler Thromb Vasc Biol. 2012;32:1936-1942. doi: 10.1161/ATVBAHA.112.251520.
71. Zhang W, Iliff JJ, Campbell CJ, Wang RK, Hurn PD, Alkayed NJ. Role of soluble epoxide hydrolase in the sex-specific vascular response to cerebral ischemia. J Cereb Blood Flow Metab. 2009;29:1475-1481. doi: 10.1038/jcbfm.2009.65.
72. Sellers KW, Sun C, Diez-Freire C, Waki H, Morisseau C, Falck JR, Hammock BD, Paton JF, Raizada MK. Novel mechanism of brain soluble epoxide hydrolase-mediated blood pressure regulation in the spontaneously hypertensive rat. FASEB J. 2005;19:626-628. doi: 10.1096/fj.04-3128fje.
73. Bianco RA, Agassandian K, Cassell MD, Spector AA, Sigmund CD. Characterization of transgenic mice with neuron-specific expression of soluble epoxide hydrolase. Brain Res. 2009;1291:60-72. doi: 10.1016/j.brainres.2009.07.060.
74. Sinal CJ, Miyata M, Tohkin M, Nagata K, Bend JR, Gonzalez FJ. Targeted disruption of soluble epoxide hydrolase reveals a role in blood pressure regulation. J Biol Chem. 2000;275:40504-40510. doi: 10.1074/jbc.M008106200.
75. Luria A, Weldon SM, Kabcenell AK, Ingraham RH, Matera D, Jiang H, Gill R, Morisseau C, Newman JW, Hammock BD. Compensatory mechanism for homeostatic blood pressure regulation in Ephx2 gene-disrupted mice. J Biol Chem. 2007;282:2891-2898. doi: 10.1074/jbc.M608057200.
76. Moulana M, Hosick K, Stanford J, Zhang H, Roman RJ, Reckelhoff JF. Sex differences in blood pressure control in SHR: lack of a role for EETs. Physiol Rep. 2014;2:. doi: 10.14814/phy2.12022.
77. Li PL, Campbell WB. Epoxyeicosatrienoic acids activate K+ channels in coronary smooth muscle through a guanine nucleotide binding protein. Circ Res. 1997;80:877-884.
78. Yang W, Tuniki VR, Anjaiah S, Falck JR, Hillard CJ, Campbell WB. Characterization of epoxyeicosatrienoic acid binding site in U937 membranes using a novel radiolabeled agonist, 20-125i-14,15-epoxyeicosa-8(Z)-enoic acid. J Pharmacol Exp Ther. 2008;324:1019-1027. doi: 10.1124/jpet.107.129577.
79. Ding Y, Frömel T, Popp R, Falck JR, Schunck WH, Fleming I. The biological actions of 11,12-epoxyeicosatrienoic acid in endothelial cells are specific to the R/S-enantiomer and require the G(s) protein. J Pharmacol Exp Ther. 2014;350:14-21. doi: 10.1124/jpet.114.214254.
80. Bukhari IA, Shah AJ, Gauthier KM, Walsh KA, Koduru SR, Imig JD, Falck JR, Campbell WB. 11,12,20-Trihydroxy-eicosa-8(Z)-enoic acid: a selective inhibitor of 11,12-EET-induced relaxations of bovine coronary and rat mesenteric arteries. Am J Physiol Heart Circ Physiol. 2012;302:H1574-H1583. doi: 10.1152/ajpheart.01122.2011.