Anti-inflammatory effects of ω-3 polyunsaturated fatty acids and soluble epoxide hydrolase inhibitors in angiotensin-II-dependent hypertension

Arzu Ulu, Todd R. Harris, Christophe Morisseau, Christina Miyabe, Hiromi Inoue, Gertrud Schuster, Hua Dong, Ana-Maria Iosif, Jun Yan Liu, Robert H Weiss, Nipavan Chiamvimonvat, John D. Imig, Bruce D. Hammock

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

The mechanisms underlying the anti-inflammatory and antihypertensive effects of long-chain ω-3 polyunsaturated fatty acids (ω-3 PUFAs) are still unclear. The epoxides of an ω-6 fatty acid, arachidonic acid epoxyeicosatrienoic acids also exhibit antihypertensive and anti-inflammatory effects. Thus, we hypothesized that the major ω-3 PUFAs, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may lower the blood pressure and attenuate renal markers of inflammation through their epoxide metabolites. Here, we supplemented mice with an ω-3 rich diet for 3 weeks in a murine model of angiotensin-II-dependent hypertension. Also, because EPA and DHA epoxides are metabolized by soluble epoxide hydrolase (sEH), we tested the combination of an sEH inhibitor and the ω-3 rich diet. Our results show that ω-3 rich diet in combination with the sEH inhibitor lowered Ang-II, increased the blood pressure, further increased the renal levels of EPA and DHA epoxides, reduced renal markers of inflammation (ie, prostaglandins and MCP-1), downregulated an epithelial sodium channel, and upregulated angiotensin-converting enzyme-2 message and significantly modulated cyclooxygenase and lipoxygenase metabolic pathways. Overall, our findings suggest that epoxides of the ω-3 PUFAs contribute to lowering systolic blood pressure and attenuating inflammation in part by reduced prostaglandins and MCP-1 and by upregulation of angiotensin-converting enzyme-2 in angiotensin-II-dependent hypertension.

Original languageEnglish (US)
Pages (from-to)285-297
Number of pages13
JournalJournal of Cardiovascular Pharmacology
Volume62
Issue number3
DOIs
StatePublished - Sep 2013

Keywords

  • ω-3 polyunsaturated fatty acids
  • Angiotensin-Idependent hypertension
  • DHA
  • EPA
  • Soluble epoxide hydrolase inhibitors

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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