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Comparing cutaneous NO-dependent vasodilation between young males and females
Preprint   Open access

Comparing cutaneous NO-dependent vasodilation between young males and females

Madison G Evering, Kelsey S Schwartz, Claire E Goebel, Anna E Stanhewicz and Jody L Greaney
medRxiv : the preprint server for health sciences
Cold Spring Harbor Laboratory
07/06/2026
DOI: 10.64898/2026.07.02.26357121
PMID: 42465875
url
https://doi.org/10.64898/2026.07.02.26357121View
This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Despite the common use of local heating and intradermal microdialysis perfusion of acetylcholine (ACh) to probe cutaneous endothelium and nitric oxide (NO)-dependent dilation, sex differences in microvascular responsiveness to these stimuli in healthy young adults remain incompletely understood.BackgroundDespite the common use of local heating and intradermal microdialysis perfusion of acetylcholine (ACh) to probe cutaneous endothelium and nitric oxide (NO)-dependent dilation, sex differences in microvascular responsiveness to these stimuli in healthy young adults remain incompletely understood.Cutaneous vasodilation was assessed in response to local heating to 39°C and 42°C and graded perfusion of ACh (10 -10 to 10 -1 mol/L) alone or concurrently with 15 mM N G -nitro-L-arginine methyl ester (L-NAME; NO synthase inhibitor) using laser-Doppler flowmetry coupled with intradermal microdialysis in 80 young adults (40 females).MethodsCutaneous vasodilation was assessed in response to local heating to 39°C and 42°C and graded perfusion of ACh (10 -10 to 10 -1 mol/L) alone or concurrently with 15 mM N G -nitro-L-arginine methyl ester (L-NAME; NO synthase inhibitor) using laser-Doppler flowmetry coupled with intradermal microdialysis in 80 young adults (40 females).Local heating to 42°C elicited greater endothelium- and NO-dependent dilation than heating to 39°C in both groups (p<0.001), but no sex differences were observed at either temperature (p=0.65). ACh-induced endothelium-dependent dilation also was not different between sexes (p=0.08), but the NO-dependent component was greater in females than in males (p=0.01). In young females, menstrual cycle day (range: day 2-33) was not associated with endothelium- or NO-dependent dilation in response to any stimulus (all p≥0.19), regardless of hormonal contraceptive use.ResultsLocal heating to 42°C elicited greater endothelium- and NO-dependent dilation than heating to 39°C in both groups (p<0.001), but no sex differences were observed at either temperature (p=0.65). ACh-induced endothelium-dependent dilation also was not different between sexes (p=0.08), but the NO-dependent component was greater in females than in males (p=0.01). In young females, menstrual cycle day (range: day 2-33) was not associated with endothelium- or NO-dependent dilation in response to any stimulus (all p≥0.19), regardless of hormonal contraceptive use.Taken together, these findings suggest that sex differences in microvascular NO bioavailability in healthy young adults depend on the stimulus used to elicit cutaneous vasodilation and, in females, microvascular endothelium- and NO-dependent dilation are not meaningfully influenced by menstrual cycle phase.ConclusionsTaken together, these findings suggest that sex differences in microvascular NO bioavailability in healthy young adults depend on the stimulus used to elicit cutaneous vasodilation and, in females, microvascular endothelium- and NO-dependent dilation are not meaningfully influenced by menstrual cycle phase.

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