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An omega‐3 epoxide of docosahexaenoic acid lowers blood pressure in angiotensin II‐dependent hypertension (832.5)
Author(s) -
Ulu Arzu,
Lee Kin Sing Stephen,
Miyabe Christina,
Yang Jun,
Hammock Bruce,
Dong Hua,
Hammock Bruce
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.832.5
Subject(s) - epoxide hydrolase 2 , epoxyeicosatrienoic acid , docosahexaenoic acid , angiotensin ii , blood pressure , arachidonic acid , chemistry , pharmacology , medicine , endocrinology , biochemistry , fatty acid , polyunsaturated fatty acid , enzyme
Mediators of anti‐hypertensive actions of docosahexaenoic acid (DHA) are largely unknown. The omega‐3 epoxide of DHA, 19, 20‐EDP (epoxydocosapentaenoic acid) is metabolized by soluble epoxide hydrolase (sEH), which also metabolizes the anti‐inflammatory and anti‐hypertensive arachidonic acid (ARA) epoxides, EETs (epoxyeicosatrienoic acids). Based in part on plasma levels of EDPs following a DHA‐rich diet, we hypothesized that 19, 20‐EDP contributes to the anti‐hypertensive actions of DHA in angiotensin‐II dependent hypertension . Treatment individually with 19, 20‐EDP, and a potent sEH inhibitor (sEHI) TPPU (1‐trifluoromethoxyphenyl‐3‐(1‐propionylpiperidin‐4‐yl) urea) significantly lowered blood pressure (BP) as compared to angiotensin‐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 mostly metabolites of the P450 pathway but also renal levels of prostaglandin‐E 2 . Our findings suggest that 19, 20‐ EDP is a mediator of the anti‐hypertensive and anti‐inflammatory effects of DHA in angiotensin‐II dependent hypertension. It appears that 19, 20‐ EDP requires metabolic stabilization with a sEHI 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. Grant Funding Source : Supported by NIEHS R01 ES002710, NIEHS Superfund Research Program grant P42 ES004699