An omega-3 epoxide of docosahexaenoic acid lowers blood pressure in angiotensin-II-dependent hypertension

Arzu Ulu, Kin Sing Stephen Lee, Christina Miyabe, Jun Yang, Bruce G. Hammock, Hua Dong, Bruce D. Hammock

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Mediators of antihypertensive actions of docosahexaenoic acid (DHA) are largely unknown. The omega-3 epoxide of DHA, 19, 20-EDP (epoxy docosapentaenoic acid), is metabolized by soluble epoxide hydrolase (sEH), which also metabolizes the anti-inflammatory and antihypertensive arachidonic acid epoxides, epoxyeicosatrienoic acids (EETs). Based in part on plasma levels of EDPs after a DHA-rich diet, we hypothesized that 19, 20-EDP contributes to the antihypertensive actions of DHA in angiotensin-II (Ang-II)-dependent hypertension. Treatment individually with 19, 20-EDP and a potent sEH inhibitor TPPU (1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea) significantly lowered blood pressure (BP) as compared with Ang-II-infused animals. The largest reduction in BP was obtained with the combination of 19, 20-EDP and TPPU, which was more efficacious than the combination of 14, 15-EET and TPPU. Oxylipin profiling revealed that 19, 20-EDP and 14, 15-EET infusion affected not only most metabolites of the P450 pathway but also renal levels of prostaglandin-E2. Our findings suggest that 19, 20-EDP is a mediator of the antihypertensive effects of DHA in Ang-II-dependent hypertension. It seems that 19, 20-EDP requires metabolic stabilization with a sEH inhibitor to be most effective in lowering BP, although both TPPU and 19, 20-EDP are so effective on their own that demonstrating additive or synergistic interactions is difficult.

Original languageEnglish (US)
Pages (from-to)87-99
Number of pages13
JournalJournal of Cardiovascular Pharmacology
Volume64
Issue number1
DOIs
StatePublished - 2014

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Keywords

  • 19,20-epoxy docosapentaenoic acid
  • angiotensin- II'dependent hypertension
  • docosahexaenoic acid
  • omega-3 polyunsaturated fatty acids
  • soluble epoxide hydrolase inhibitors

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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