NYMC Faculty Publications

Inhibition of Soluble Epoxide Hydrolase Reduces Portal Pressure by Protecting Mesenteric Artery Myogenic Responses in Cirrhotic Rats

DOI

10.1016/j.prostaglandins.2017.03.007

Journal Title

Prostaglandins & Other Lipid Mediators

First Page

17

Last Page

24

Document Type

Article

Publication Date

July 2017

Department

Physiology

Abstract

Hyperdynamic circulation contributes to the progress of portal hypertension in liver cirrhosis. We investigated the effects of soluble epoxide hydrolase (sEH) inhibition on portal pressure and the myogenic response of mesenteric arteries isolated from cirrhotic rats using the sEH inhibitor t-TUCB (trans-4-{4-[3-(4-trifluoromethoxyphenyl)-ureido]cyclohexyloxy}benzoic acid). Cirrhotic tissues had a higher ratio of epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs) following increased CYP2C11 expression, which may be a protective response. In comparison with controls, myogenic responses of mesenteric arteries from cirrhotic rats were attenuated at 80-140mmHg, while inhibition of sEH partly reversed the impaired myogenic constriction at 100-140mmHg and exhibited better feedback of vascular smooth muscle to pressure variation. Inhibition of sEH reduced portal pressure by decreasing endothelial synthesis of nitric oxide. An imbalance between EETs and nitric oxide may account for hyperdynamic circulation. sEH inhibitors may provide a novel approach for treating cirrhosis of the liver.

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