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Impact of P450 eicosanoids on bioavailability of NO in the vasculature of mice
Author(s) -
Gollasch Maik,
Hercule Hantz C.,
Schunck WolfHagen,
Gross Volkmar,
Seringer Jasmin,
Leung Fung Ping,
Costa Goncalves Andrey Ch.,
Huang Yu,
Luft Friedrich C.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.952.2
Subject(s) - epoxide hydrolase 2 , chemistry , mesenteric arteries , apamin , vasodilation , charybdotoxin , pharmacology , endothelium derived hyperpolarizing factor , bradykinin , nitric oxide , epoxyeicosatrienoic acid , endothelium , medicine , potassium channel , endocrinology , artery , biochemistry , arachidonic acid , enzyme , receptor , organic chemistry
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. 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 plus charybdotoxin (ChTx). All four EETs (5,6‐EET, 8,9‐EET, 11,12‐EET, 14,15‐EET) (total 243 +/‐ 56 ng/g, ratio 52:16:11:21) were present in the vessel wall of mesenteric arteries. All four EETs (order of potency: 8,9‐EET>14,15‐EET~5,6‐EET>11,12‐EET) and all four dihydroxy derivatives (14,15‐DHET~8,9‐DHET~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 μg/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. 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 release. This pathway may increase in importance during cardiovascular disease, when NO production is reduced.