Sex differences in mouse aortic relaxation via estrogen receptor signaling (680.17)

Cardiovascular disease is the leading cause of death both in the United States and worldwide. Estrogen receptors (ERs) have been previously shown to mediate the mechanisms responsible for playing cardioprotective roles. However, the effect of sex on estrogen receptor‐mediated vascular function is not well‐understood. We investigated the effect of the ER‐alpha agonist, PPT on phenylephrine (Phe; 10 ‐6 M)‐precontracted male and female mouse aortic rings in the presence and absence of the ER‐alpha antagonist, MPP, ERK1/2 inhibitor, PD98059, and + K‐ATP channel blocker, glibenclamide. We found that PPT induced aortic relaxation in both male and female endothelial‐intact mouse aortic rings at concentrations of 100 μM (62% ± 4 for males vs. 86.6% ± 5 for females) and 1000 μM (70% ± 6 for males vs. 99.9% ± 6 for females), respectively. However, in endothelium‐denuded mouse aortas, PPT‐induced relaxation was attenuated in both males and females, and there were no sex differences. MPP obviated PPT‐induced aortic relaxation (100 μM) in endothelial‐intact mouse aortas. Further, attenuated PPT‐induced aortic relaxation was observed when treated with PD98059 or glibenclamide in endothelial‐intact male and female aortas. In summary, we present potential sex differences in estrogen receptor‐mediated mechanisms for aortic relaxation involving ERK1/2 and the + K‐ATP channel. Grant Funding Source : 5K12HD043451