Vanderbilt Translational Research Forum

2019 Guest Speaker

Suzanne Oparil, MD
2019 Guest Speaker

SO Picture 2008 JPEG (Lg 168kb)Research in Dr. Oparil’s laboratory spans the gamut from molecular and cellular studies to the whole animal to clinical trials. This work has two general themes: 1) the pathogenesis of vascular disease, with particular emphasis on sexual dimorphism and the protective effects of female sex hormones and 2) the pathophysiology and treatment of high blood pressure. Dr. Oparil and colleagues have demonstrated a sexual dimorphism in the development of both high blood pressure and atherosclerotic vascular disease. In both cases, females are protected from vascular damage related to high blood pressure and other stimuli compared to males. Oparil and colleagues have determined that vasoprotection related to female sex is due to the presence of estrogen and is somewhat opposed by progestins. They have recently defined a novel pathway by which blood vessels respond to mechanical injury, i.e., activation of cells in the outer-most layer of the blood vessel, the adventitia. Activated adventitial cells begin to divide and then migrate toward the luminal surface of the vessel, contributing to the injury response, or vascular “scar” formation. The Oparil laboratory has defined a specific pathway by which estrogen protects against adventitial activation and the movement of adventitial cells into the area of injury. This novel mechanism provides a tantalizing target for future gene therapy.

Dr. Oparil, in collaboration with colleagues at UAB, has developed and characterized a model of salt-sensitive hypertension in the spontaneously hypertensive rat (SHRS). Using this model, they have demonstrated that the nervous system contributes importantly to the development of salt sensitive hypertension. Past studies have shown that in the SHR-S, excessive dietary salt leads to a significant selective decrease in noradrenaline release from nerve terminals in the anterior hypothalamic area. This in turn causes decreased inhibition of sympathetic nervous system activity and a resultant rise in arterial pressure. Current studies are elucidating the mechanisms by which the anterior hypothalamus plays a role in salt sensitive hypertension.

As a corollary to the above basic science studies, Dr. Oparil and colleagues have initiated and/or participated in over 50 clinical trials involving patients with forms of essential hypertension, congestive heart failure, peripheral vascular disease, hyperlipidemia and diabetes mellitus. They have a fully equipped clinical research unit specifically qualified to deal with these important disease entities.

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