Sun D, Cuevas AJ, Gotlinger K, Hwang SH, Hammock BD, Schwartzman ML, Huang A. Soluble epoxide hydrolase-dependent regulation of myogenic response and blood pressure. Am J Physiol Heart Circ Physiol 306: H1146-H1153, 2014. First published February 21, 2014 doi:10.1152/ajpheart.00920.2013 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. myogenic response; soluble epoxide hydrolase; epoxyeicosatrienoic acids; arterioles; endothelium THE ISSUE OF HOW THE VASCULAR system maintains basal tone and regulates blood supply and organ perfusion, as well as capillary hydrostatic pressure, has been extensively investigated. Among the above-mentioned functions, the vascular myogenic response is a key contributor. The myogenic response is characterized by the intrinsic ability of small arteries/arterioles to contract in response to increases in transmural pressure. In physiological conditions, the myogenic response functions as an autoregulator that allows the vascular bed to maintain a constant blood flow despite wide changes in arterial pressure. In certain pathological conditions, however, augmented myogenic response initiates an increase in peripheral resistance and consequently increases the risk of hypertension. On the other hand, attenuated myogenic response may exhibit beneficial properties in the regulation of blood pressure, such as an estrogen...