CYP1A1 efficiently metabolizes omega 3 (n-3) polyunsaturated fatty acids (PUFAs) and may play a role in the increase of nitric oxide (NO)–dependent blood pressure regulation and vasodilation related to an n-3 PUFA diet. In this study, CYP1A1 wild-type (WT) and knockout (KO) mice were fed an n-3 or n-6 PUFA–enriched diet. KO mice on the n-3 PUFA diet accumulated significantly higher levels of n-3 PUFAs in 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, acetylcholine-mediated vasodilation in mesenteric arterioles on both diets. Finally, the n-3 PUFA diet significantly increased aortic phospho-Ser1177-endothelial NO synthase (eNOS)/eNOS ratio in 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.
See article at J Pharmacol Exp Ther 2014, 351:688–698.
- Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics