Advancing age and loss of ovarian hormones impair flow‐induced dilation in the female coronary microvasculature

Abstract

Prior to menopause, the progression of cardiovascular disease with age is more rapid in men than in women; however, it remains unknown whether the cardiovascular protection experienced by premenopausal women is due to the presence of ovarian hormones. We tested the hypothesis that endothelium‐dependent dilation is impaired with advancing age in coronary arterioles from female rats, and would be further impaired by a decline in or removal of estrogen. Coronary arterioles were isolated from young (6 mo), middle‐aged (14 mo), and old (24 mo) control, ovariectomized (OVX), and OVX + estrogen‐replacement (OVE) Fischer‐344 female rats to assess dilation to flow (FID) and dea‐NONO‐ate. FID was greater in arterioles from young and middle‐aged control rats as compared to old control rats. OVX decreased FID in arterioles from young and middle‐aged rats, but had no effect in aged rats. Conversely, OVE restored or improved FID in arterioles from OVX rats as compared to control rats. Protein and mRNA expression of AKT and eNOS, both key signaling proteins in FID, were significantly reduced in coronary arterioles from old control and OVX rats. Dea‐NONO‐ate, an exogenous NO donor, produced similar vasodilation in all groups. These data indicate that endothelium‐dependent FID is impaired with advancing age in coronary arterioles from female rats, and estrogen‐replacement can improve or restore FID in OVX rats. NIH: HL077224‐02.