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Interaction between P450 eicosanoids and nitric oxide in the control of arterial tone in mice

Item Type:Article
Title:Interaction between P450 eicosanoids and nitric oxide in the control of arterial tone in mice
Creators Name:Hercule, H.C. and Schunck, W.H. and Gross, V. and Seringer, J. and Leung, F.P. and Weldon, S.M. and da Costa Goncalves, A.C. and Huang, Y. and Luft, F.C. and Gollasch, M.
Abstract:OBJECTIVE: Epoxyeicosatrienoic acids (EETs) serve as endothelial-derived hyperpolarizing factors (EDHF), but may also affect vascular function by other mechanisms. We identified a novel interaction between EETs and endothelial NO release using soluble epoxide hydrolase (sEH) -/- and +/+ mice. METHODS AND RESULTS: EDHF responses to acetylcholine in pressurized isolated mesenteric arteries were neither affected by the sEH inhibitor, N-adamantyl-N'-dodecylurea (ADU), nor by sEH gene deletion. However, the EDHF responses were abolished by catalase and by apamin/charybdotoxin (ChTx), but not by iberiotoxin, nor by the cytochrome P450 inhibitor PPOH. All four EETs (order of potency: 8,9-EET >14,15-EET approximately 5,6-EET >11,12-EET) and all 4 dihydroxy derivatives (14,15-DHET approximately 8,9-DHET approximately 11,12-DHET >5,6-DHET) produced dose-dependent vasodilation. Endothelial removal or L-NAME blocked 8,9-EET and 14,15-DHET-dependent dilations. The effects of apamin/ChTx were minimal. 8,9-EET and 14,15-DHET induced NO production in endothelial cells. ADU (100 microg/mL in drinking water) lowered blood pressure in angiotensin II-infused hypertension, but not in L-NAME-induced hypertension. Blood pressure and EDHF responses were similar in L-NAME-treated sEH +/+ and -/- mice. CONCLUSIONS: Our data indicate that the EDHF response in mice is caused by hydrogen peroxide, but not by P450 eicosanoids. Moreover, P450 eicosanoids are vasodilatory, largely through their ability to activate endothelial NO synthase (eNOS) and NO release.
Keywords:Eicosanoids, Soluble Epoxide Hydrolase, NO Synthase, L-NAME, EDRF, Animals, Mice
Source:Arteriosclerosis Thrombosis and Vascular Biology
Publisher:American Heart Association
Page Range:54-60
Date:January 2009
Official Publication:https://doi.org/10.1161/ATVBAHA.108.171298
PubMed:View item in PubMed

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