Vascular Biology Laboratory
Premenopausal females have a lower incidence of many cardiovascular diseases, including hypertension. Because this protection steeply declines after menopause, we know that estrogen is at least partially responsible for these beneficial effects. In the vasculature, estrogen alters the expression of a variety of genes including hormone receptors, growth factors, and extracellular matrix proteins and also directly promotes smooth muscle cell relaxation. There are two known estrogen receptor subtypes that mediate the genomic actions of the steroid; however, it is not known whether the newly discovered estrogen receptor GPR30 contributes to estrogen’s cardioprotective effects. Previous results from this laboratory show that in congenic mRen2 rats, a model of angiotensin II-dependent hypertension, females display only mild increases in blood pressure in comparison to males unless ovariectomized. This unique estrogen-sensitive model appropriately reflects the higher blood pressure seen in postmenopausal women.
This laboratory utilizes a unique angiotensin II-dependent, estrogen-sensitive, and salt-sensitive rodent model of hypertension to dissect the mechanisms by which GPR30 mediates its cardiovascular effects. We take an integrative approach by utilizing an in vitro cell culture system, an ex vivo isolated resistance vessel preparation, and in vivo analysis of the congenic mRen2 hypertensive animal to assess the acute and chronic interactions of GPR30 and the renin-angiotensin system.