Sex Steroids and Gender in Cardiovascular-Renal Physiology and Pathophysiology: Sex differences in endothelin-1-mediated vasoconstrictor tone in middle-aged and older adults

摘要

The prevalence of cardiovascular disease is lower in middle-aged and older women than men. Increased endothelin-1-mediated vasoconstriction has been linked to the etiology of a number of cardiovascular diseases, including atherosclerosis, heart failure, and hypertension. It is unknown whether a sex difference in endothelin-1-mediated vasoconstrictor tone exists in middle-aged and older adults. Therefore, we tested the hypothesis that middle-aged and older men would demonstrate greater ET-1-mediated vasoconstrictor tone than age-matched women. Forearm blood flow in response to intra-arterial infusions of endothelin (ET)-1, BQ-123 (a selective ETA receptor antagonist), and BQ-788 (a selective ETB receptor antagonist) was assessed by venous occlusion plethysmography in 21 women (age: 58 ± 1 yr; body mass index: 26.0 ± 1.0 kg/m²) and 25 men (age: 57 ± 2 yr; body mass index: 26.8 ± 0.7 kg/m²). In response to BQ-123, the increase in forearm blood flow from baseline was significantly higher in the men than the women (24 ± 5% vs. 9 ± 5%; P < 0.05). In contrast, the increase in forearm blood flow in response to BQ-123 coinfused with BQ-788 was greater in the women than the men, such that the maximum vasodilation to dual endothelin receptor blockade was similar between men and women (∼25%). There was no difference in the vasoconstrictor response to ET-1 between the sexes. These results indicate that middle-aged and older men are under greater ETA receptor-mediated vasoconstrictor tone than age-matched women. Since the ETA receptor is the predominant receptor subtype in the coronary vasculature, this sex difference in vasoconstrictor tone may be a mechanism contributing to the sex difference in the prevalence of coronary heart disease in middle-aged and older adults.