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

Am J Physiol Regul Integr Comp Physiol. 2010 Feb;298(2):R261-5. doi: 10.1152/ajpregu.00626.2009. Epub 2009 Nov 25.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Body Composition / physiology
  • Body Mass Index
  • Endothelin A Receptor Antagonists
  • Endothelin-1 / administration & dosage
  • Endothelin-1 / pharmacology*
  • Female
  • Forearm / blood supply
  • Humans
  • Infusions, Intra-Arterial
  • Lipids / blood
  • Male
  • Middle Aged
  • Muscle Tonus / drug effects*
  • Muscle, Smooth, Vascular / drug effects*
  • Norepinephrine / pharmacology
  • Oligopeptides / pharmacology
  • Peptides, Cyclic / pharmacology
  • Piperidines / pharmacology
  • Receptor, Endothelin B / drug effects
  • Regional Blood Flow / drug effects
  • Sex Characteristics
  • Vasoconstrictor Agents / administration & dosage
  • Vasoconstrictor Agents / pharmacology*


  • Endothelin A Receptor Antagonists
  • Endothelin-1
  • Lipids
  • Oligopeptides
  • Peptides, Cyclic
  • Piperidines
  • Receptor, Endothelin B
  • Vasoconstrictor Agents
  • BQ 788
  • cyclo(Trp-Asp-Pro-Val-Leu)
  • Norepinephrine