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National Institute of Environmental Health Sciences

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Publication Detail

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

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

Published In J Cardiovasc Pharmacol, (2014 Jul)

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.

PubMed ID: 24691274 Exiting the NIEHS site

MeSH Terms: Angiotensin II/metabolism; Animals; Antihypertensive Agents/pharmacology*; Blood Pressure/drug effects; Docosahexaenoic Acids/pharmacology*; Epoxide Hydrolases/metabolism; Fatty Acids, Omega-3/pharmacology*; Hypertension/drug therapy*; Hypertension/physiopathology; Male; Mice; Phenylurea Compounds/pharmacology; Piperidines/pharmacology

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