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Published on: June 3, 2019
Sex differences in endothelin-1-mediated vasoconstrictor tone in middle-aged and older adults
Brian L Stauffer1, Christian M Westby, Jared J Greiner
1Integrative Vascular Biology Laboratory, Dept. of Integrative Physiology, Univ. of Colorado, 354 UCB, Boulder, CO 80309, USA. Brian.Stauffer@ucdenver.edu
Insights
Middle-aged men exhibit greater endothelin-1 (ET-1) mediated vasoconstriction via ET(A) receptors than women. This sex difference in vasoconstrictor tone may contribute to higher coronary heart disease prevalence in men.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Sex Differences in Disease
Background:
- Cardiovascular disease (CVD) prevalence is lower in women than men, particularly in middle age and beyond.
- Increased vasoconstriction mediated by endothelin-1 (ET-1) is implicated in CVD pathogenesis, including atherosclerosis, heart failure, and hypertension.
- Existing research has not clarified if sex-based differences in ET-1 mediated vasoconstrictor tone exist in older adults.
Purpose of the Study:
- To investigate potential sex differences in endothelin-1 (ET-1) mediated vasoconstrictor tone in middle-aged and older adults.
- To test the hypothesis that men exhibit greater ET-1 mediated vasoconstrictor tone compared to age-matched women.
- To explore the roles of ET(A) and ET(B) receptors in mediating these sex differences.
Main Methods:
- Forearm blood flow was measured using venous occlusion plethysmography in 21 women and 25 men (ages 57-58).
- Intra-arterial infusions of endothelin-1 (ET-1), the selective ET(A) receptor antagonist BQ-123, and the selective ET(B) receptor antagonist BQ-788 were administered.
- Vasoconstrictor and vasodilator responses were assessed by analyzing changes in forearm blood flow.
Main Results:
- No significant sex difference was observed in the vasoconstrictor response to direct ET-1 infusion.
- Men showed a significantly greater increase in forearm blood flow in response to the ET(A) receptor antagonist BQ-123 compared to women (24% vs. 9%).
- Dual blockade of ET(A) and ET(B) receptors resulted in similar maximal vasodilation between sexes, indicating comparable overall endothelin system contribution.
Conclusions:
- Middle-aged and older men experience greater vasoconstriction mediated by the ET(A) receptor compared to age-matched women.
- The ET(A) receptor's predominant role in coronary vasculature suggests this sex difference may underlie the higher prevalence of coronary heart disease in men.
- Understanding these sex-specific mechanisms is crucial for targeted cardiovascular disease prevention and treatment strategies.
Abstract:
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 ET(A) receptor antagonist), and BQ-788 (a selective ET(B) receptor antagonist) was assessed by venous occlusion plethysmography in 21 women (age: 58 + or - 1 yr; body mass index: 26.0 + or - 1.0 kg/m(2)) and 25 men (age: 57 + or - 2 yr; body mass index: 26.8 + or - 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 + or - 5% vs. 9 + or - 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 (approximately 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 ET(A) receptor-mediated vasoconstrictor tone than age-matched women. Since the ET(A) 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.
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