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Research ArticleCardiovascular

Role of Cytochrome P4501A1 in Modulating the Vascular and Blood Pressure Benefits of Omega-3 Polyunsaturated Fatty Acids

Larry N Agbor, Elani F Wiest, Michael Rothe, Wolf-Hagen Schunck and Mary K Walker
Journal of Pharmacology and Experimental Therapeutics October 14, 2014, jpet.114.219535; DOI: https://doi.org/10.1124/jpet.114.219535
Larry N Agbor
University of New Mexico;
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Elani F Wiest
University of New Mexico;
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Michael Rothe
Lipidomix GmbH;
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Wolf-Hagen Schunck
Max Delbrueck Center for Molecular Medicine
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Mary K Walker
University of New Mexico;
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Abstract

The mechanisms that mediate the cardiovascular protective effects of omega 3 (n-3) polyunsaturated fatty acids (PUFAs) have not been fully elucidated. Cytochrome P4501A1 (CYP1A1) 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 eight 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 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 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 to 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.

  • blood pressure
  • CYP1A
  • fatty acid metabolism
  • nitric oxide
  • vasodilators
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 365 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 365, Issue 2
1 May 2018
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Research ArticleCardiovascular

Role of Cytochrome P4501A1 in Modulating the Vascular and Blood Pressure Benefits of Omega-3 Polyunsaturated Fatty Acids

Larry N Agbor, Elani F Wiest, Michael Rothe, Wolf-Hagen Schunck and Mary K Walker
Journal of Pharmacology and Experimental Therapeutics October 14, 2014, jpet.114.219535; DOI: https://doi.org/10.1124/jpet.114.219535

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Research ArticleCardiovascular

Role of Cytochrome P4501A1 in Modulating the Vascular and Blood Pressure Benefits of Omega-3 Polyunsaturated Fatty Acids

Larry N Agbor, Elani F Wiest, Michael Rothe, Wolf-Hagen Schunck and Mary K Walker
Journal of Pharmacology and Experimental Therapeutics October 14, 2014, jpet.114.219535; DOI: https://doi.org/10.1124/jpet.114.219535
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