Sex differences in endothelin-1-mediated vasoconstrictor tone in middle-aged and older adults.
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.
Stauffer
Brian L
BL
Integrative Vascular Biology Laboratory, Dept. of Integrative Physiology, Univ. of Colorado, 354 UCB, Boulder, CO 80309, USA. Brian.Stauffer@ucdenver.edu
Westby
Christian M
CM
Greiner
Jared J
JJ
Van Guilder
Gary P
GP
Desouza
Christopher A
CA
D000368:Aged; D001823:Body Composition / Q000502:physiology; D015992:Body Mass Index; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007261:Infusions, Intra-Arterial; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009129:Muscle Tonus / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D044023:Receptor, Endothelin B / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D012727:Sex Characteristics; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*
D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D008055:Lipids; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D044023:Receptor, Endothelin B; D014662:Vasoconstrictor Agents; C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D009638:Norepinephrine