Abstract P620: Aging Decreases Vascular GPER Expression and Function

Abstract

Menopause accelerates the development of hypertension, arterial stiffness, end organ damage, and diastolic dysfunction. Postmenopausal hormone therapy relieves menopausal symptoms but promotes adverse cardiovascular outcomes, which may be due to aging-induced alterations in estrogen receptors. We previously published that GPER expression as well as agonist-induced vasorelaxation is decreased in mesenteric arteries from 12 month-old mRen2 female rats. We hypothesized that aging-induced GPER downregulation is present in other rodent species and strains as well. Aortas from young (2-3 months) and aged (11-23 months) C57BL/6 and BALB/c mice were lysed and immunoblotted for GPER protein. In addition, mesenteric arteries from C57BL/6 mice were mounted on a wire myograph and assessed for vasorelaxation in response to estrogen receptor agonists. We found a significant downregulation of GPER in aging aortas (3.1 ± 0.6 vs. 0.63 ± 0.42, P=0.016, N=4 per group). Moreover, we found that vasodilation to the GPER agonist G-1 was significantly attenuated in aging resistance arteries (22 ± 7.5% vs 58 ± 6.5%, P=0.023, N=2-4). Interestingly, vasodilation to the nonselective receptor agonist estradiol was not altered by aging (24 ± 10% vs. 32 ± 2.0%, P=0.23, N=2-4). In light of our previous findings in the rat vasculature, our data indicate that aging-induced decreases in vascular GPER expression and function are conserved across vascular beds and rodent species. We propose that aging-induced GPER downregulation switches the vascular benefits of postmenopausal estrogen therapy from positive to negative. Our future goal is to determine whether therapies that target GPER improve cardiovascular outcomes to protect the aging female population.