Role of CYP1A1 in modulating the vascular and blood pressure benefits of omega-3 polyunsaturated fatty acids

Item Type:	Article
Title:	Role of CYP1A1 in modulating the vascular and blood pressure benefits of omega-3 polyunsaturated fatty acids
Creators Name:	Agbor, L.N. and Wiest, E.F. and Rothe, M. and Schunck, W.H. and Walker, M.K.
Abstract:	The mechanisms that mediate the cardiovascular protective effects of omega 3 (n-3) polyunsaturated fatty acids (PUFAs) have not been fully elucidated. Cytochrome P450 1A1 efficiently metabolizes n-3 PUFAs to potent vasodilators. Thus, we hypothesized that dietary n-3 PUFAs increase nitric oxide (NO)-dependent blood pressure regulation and vasodilation in a CYP1A1-dependent manner. CYP1A1 wild-type (WT) and knockout (KO) mice were fed an n-3 or n-6 PUFA-enriched diet for 8 weeks and were analyzed for tissue fatty acids and metabolites, NO-dependent blood pressure regulation, NO-dependent vasodilation of acetylcholine (ACh) in mesenteric resistance arterioles, and endothelial NO synthase (eNOS) and phospho-Ser1177-eNOS expression in the aorta. All mice fed the n-3 PUFA diet showed significantly higher levels of n-3 PUFAs and their metabolites, and significantly lower levels of n-6 PUFAs and their metabolites. In addition, KO mice on the n-3 PUFA diet accumulated significantly higher levels of n-3 PUFAs in the aorta and kidney without a parallel increase in the levels of their metabolites. Moreover, KO mice exhibited significantly less NO-dependent regulation of blood pressure on the n-3 PUFA diet and significantly less NO-dependent, ACh-mediated vasodilation in mesenteric arterioles on both diets. Finally, the n-3 PUFA diet significantly increased aortic phospho-Ser1177-eNOS/eNOS ratio in the WT compared with KO mice. These data demonstrate that CYP1A1 contributes to eNOS activation, NO bioavailability, and NO-dependent blood pressure regulation mediated by dietary n-3 PUFAs.
Keywords:	Blood Pressure, Cytochrome P-450 CYP1A1, Inbred C57BL Mice, Knockout Mice, Nitric Oxide, Omega-3 Fatty Acids, Vasodilation, Animals, Mice
Source:	Journal of Pharmacology and Experimental Therapeutics
ISSN:	0022-3565
Publisher:	American Society for Pharmacology and Experimental Therapeutics
Volume:	351
Number:	3
Page Range:	688-698
Date:	December 2014
Official Publication:	https://doi.org/10.1124/jpet.114.219535
PubMed:	View item in PubMed

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