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Angiotensin II type 2 receptor-mediated dilation is greater in the cutaneous microvasculature of premenopausal women compared to men
Journal article   Peer reviewed

Angiotensin II type 2 receptor-mediated dilation is greater in the cutaneous microvasculature of premenopausal women compared to men

Kelsey S. Schwartz, James A. Lang and Anna E. Stanhewicz
Journal of applied physiology (1985), Vol.135(6), pp.1236-1242
12/01/2023
DOI: 10.1152/japplphysiol.00382.2023
PMCID: PMC11918385
PMID: 37823205
url
https://www.ncbi.nlm.nih.gov/pmc/articles/11918385View
Open Access

Abstract

Differential activation of the renin-angiotensin system (RAS) likely contributes to sex differences in cardiovascular outcomes in premenopausal women compared to age-matched men. Women demonstrate reduced activation of the vasoconstrictor angiotensin II type 1 receptors (AT 1 R) compared to men, and evidence suggests women also likely have increased sensitivity of the vasodilatory angiotensin II type 2 receptors (AT 2 R). However, few in vivo studies have directly examined sex differences in AT 2 R-mediated dilation, or the balance between AT 1 R- and AT 2 R-mediated vascular responses in humans. Using the cutaneous microcirculation as a model, we hypothesized that AT 2 R-mediated dilation would be greater in premenopausal women compared to men, and that AT 1 R-blockade would augment AT 2 R-mediated dilation to a greater extent in men than in women. 12 healthy women (22±3 yrs) and 12 men (23±5 yrs) had two intradermal microdialysis fibers placed in the ventral forearm for graded infusions of compound 21 (AT 2 R agonist; 10 -12 -10 -8 M) in a control fiber site and a site treated with 43µM losartan (AT 1 R antagonist). Red blood cell flux was measured continuously by laser-Doppler flowmetry, and cutaneous vascular conductance (CVC=flux/MAP) was normalized to maximum (%max; 28mM SNP+43°C). Women had greater AT 2 R-mediated dilation compared to men (women: 25±4 vs. men: 15±2%max, p=0.03). Local AT 1 R inhibition increased AT 2 R-mediated dilation in men (losartan: 26±4 vs. control: 15±2%max, p<0.001) but had no effect in women (losartan: 27±6 vs. control: 25±4%max, p>0.05). These data suggest that premenopausal women have a greater AT 2 R-mediated vasodilation response than men, and that AT 1 R activation inhibits AT 2 R-mediated dilation in men, but not in women.
 angiotensin II microvasculature sex differences vasodilation

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