Sex differences in endothelin-1-mediated vasoconstrictor tone in middle-aged and older adults

Stauffer BL, Westby CM, Greiner JJ, Van Guilder GP, DeSouza CA. Sex differences in endothelin-1-mediated vasoconstrictor tone in middle-aged and older adults. Am J Physiol Regul Integr Comp Physiol 298: R261-R265, 2010. First published November 25, 2009; doi:10.1152/ajpregu.00626.2009.-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/m(2)) and 25 men (age: 57 +/- 2 yr; body mass index: 26.8 +/- 0.7 kg/m(2)). 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 (similar to 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.