Abstract 189: Hypercholesterolemia Blunts Gender Differences in Vascular Endothelin-1 Activity in Middle-Aged Adults

Abstract

Background: Compared with age-matched women, healthy middle-aged men have a higher vascular activity of the vasoconstrictor and proatherosclerotic peptide endothelin-1(ET-1). Hypercholesterolemia is a major atherosclerotic risk factor and is associated with increased ET-1 activity. Whether high cholesterol levels abrogate gender differences in vascular ET-1 activity has not been studied. This investigation has been conducted to test the hypothesis that hypercholesterolemia blunts the gender difference in ET-1 activity present in middle-aged men and women. Methods: Forearm blood flow (FBF) responses were measured by strain-gauge plethysmography during the intra-arterial infusion of the selective ET A receptor blocker BQ-123 in 19 women and 21 men with hypercholesterolemia (total cholesterol >240 mg/dL). Results: Baseline characteristics were similar between women and men (see table). BQ-123 administration resulted in a significant progressive vasodilator response in both the female and male group (p < 0.001 for both). When these responses were compared between the two gender groups, no significant differences were observed (p=NS). Conclusions: Hypercholesterolemia increases the vascular activity of ET-1 in middle-aged women and men. The lack of difference in ET-1 activity between women and men suggests that hypercholesterolemia eliminates the gender differences in ET-1 vascular activity, potentially offsetting the advantage in cardiovascular risk of middle-aged women compared with middle-aged men.