- Author: Kathy Keatley Garvey
Titled “The Role of EETs in Pressure-induced Vasoconstriction,” the podcast explains the ground-breaking research involving the role of EETs (Epoxyeicosatrienoic acids) in regulating the myogenic tone in a skeletal muscle small resistance artery. The research, done on rodents, could lead to better control of high blood pressure in humans.
In the podcast, associate editor Mordy Blaustein interviews lead author An Huang (New York Medical College) and expert David Harder (Medical College of Wisconsin) about what Blaustein describes as “an innovative knock-out mouse model, responses of different types of vascular beds to various vasodilatory agents, and the importance of basic studies on SEH inhibitors as the backbone of clinical trials.”
EETs possess cardioprotective properties that are “catalyzed by soluble epoxide hydrolase (sEH) to dihydroxyeicosatrienoic acids (DHETs) that lack vasoactive property,” the seven-member scientific team wrote in their research, Soluble epoxide hydrolase-dependent regulation of myogenic response and blood pressure, published April 15 in the American Journal of Physiology-Heart and Circulatory Physiology.
“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,” they wrote in their abstract. “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.”
Lead author An Huang is with the Department of Physiology, New York Medical College, Valhalla.
In addition to Huang and Hammock, who has a joint appointment with the UC Davis Comprehensive Cancer Center, the co-authors are Sung Hee Hwang of the Hammock lab; Dong Sun, Department of Physiology, New York Medical College, Valhalla; Azita J. Cuevas and Michal L. Schwartzman, both with the Department of Pharmacology, New York Medical College, Valhalla; and Katherine Gotlinger, New York University School of Medicine, Tuxedo.
Grants from the by National Institutes of Health supported the research.