NYMC Faculty Publications

Soluble Epoxide Hydrolase-Dependent Regulation of Myogenic Response and Blood Pressure

Author Type(s)

Faculty

DOI

10.1152/ajpheart.00920.2013

Journal Title

American Journal of Physiology

First Page

1146

Last Page

1153

Document Type

Article

Publication Date

4-15-2014

Department

Physiology

Keywords

Animals, Arachidonic Acids, Arterioles, Benzoates, Blood Pressure, Cardiotonic Agents, Cytochrome P-450 CYP4A, Cytochrome P-450 Enzyme System, Cytochrome P450 Family 2, Endothelium, Vascular, Enzyme Inhibitors, Epoxide Hydrolases, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Muscle Development, Nitric Oxide Synthase Type III, Phenylurea Compounds, Vasoconstriction, Vasodilation

Disciplines

Medicine and Health Sciences

Abstract

Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid via cytochrome P450 (CYP)/epoxygenases. EETs possess cardioprotective properties and are catalyzed by soluble epoxide hydrolase (sEH) to dihydroxyeicosatrienoic acids (DHETs) that lack vasoactive property. To date, the role of sEH in the regulation of myogenic response of resistant arteries, a key player in the control of blood pressure, remains unknown. To this end, experiments were conducted on sEH-knockout (KO) mice, wild-type (WT) mice, and endothelial nitric oxide synthase (eNOS)-KO mice treated with t-TUCB, a sEH inhibitor, for 4 wk. sEH-KO and t-TUCB-treated mice displayed significantly lower blood pressure, associated with significantly increased vascular EETs and ratio of EETs/DHETs. Pressure-diameter relationships were assessed in isolated and cannulated gracilis muscle arterioles. All arterioles constricted in response to increases in transmural pressure from 60 to 140 mmHg. The myogenic constriction was significantly reduced, expressed as an upward shift of pressure-diameter curve, in arterioles of sEH-KO and t-TUCB-treated eNOS-KO mice compared with their controls. Removal of the endothelium, or treatment of the vessels with PPOH, an inhibitor of EET synthase, restored the attenuated pressure-induced constriction to the levels similar to those observed in their controls but had no effects on control vessels. No difference was observed in the myogenic index, or in the vascular expression of eNOS, CYP2C29 (EET synthase), and CYP4A (20-HETE synthase) among these groups of mice. In conclusion, the increased EET bioavailability, as a function of deficiency/inhibition of sEH, potentiates vasodilator responses that counteract pressure-induced vasoconstriction to lower blood pressure.

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