No impact of biological sex on nitric oxide contribution to cutaneous vascular response to 39ºC local heating

Abstract

Purpose: The contribution of endothelial nitric oxide (NO) to vasodilation (%NO contribution) is a significant indicator of risk of cardiovascular disease development. Local skin heating to either 42 ºC or 39 ºC is used to determine mechanisms of vasodilation in health and disease, specifically to investigate %NO contribution. Women have lower %NO contribution in the cutaneous vasculature than men in the early follicular phase of the menstrual cycle, when the circulating vasoactive reproductive hormones are at their lowest concentration. However, this phase represents only a brief portion of the menstrual cycle. We aimed to determine the overall impact of biological sex on %NO contribution to cutaneous vasodilation utilizing a 39ºC local heating protocol, which better isolates the endothelial NO-synthase pathway. We tested women randomly during any phase of the menstrual cycle. We hypothesized that women would demonstrate greater NO-dependent cutaneous vasodilation than men in response to 39ºC local heating. Methods: Data are represented as mean(SD). An intradermal microdialysis fiber was placed in the ventral forearms of 12 men and 13 women [24.2(4.6) years]. Local heaters and laser-Doppler flowmetry probes were used to measure red blood cell flux (perfusion units, PU). Cutaneous vascular conductance (CVC) was calculated as laser-Doppler PU/mean arterial pressure. A standard 39ºC local heating protocol was conducted wherein PU was continuously collected at rest (10 minutes), then the local temperature was increased to 39ºC. After PU reached a steady plateau (~40 minutes), the NO synthase inhibitor 15 mM NG-nitro-L-arginine methyl ester (L-NAME) was perfused. Maximal vasodilation was induced by heating to 43ºC and perfusing 28 mM sodium nitroprusside and normalized to %CVCmax. %NO contribution was calculated as the absolute percentage difference between %CVCmax of 39ºC plateau and %CVCmax of L-NAME steady-state. We compared both CVC and %CVCmax between groups with two-way ANOVA and the %NO contribution with unpaired t-tests. Results: The %NO contribution was not different between sexes [men 48(23)%, women 39(17)%; P = 0.26]. There was no effect of sex on either absolute CVC [men 0.717(0.29) PU, women 0.73(0.48) PU at 39ºC phase] or %CVCmax [men 69(31)%, women 54(20)% at 39ºC phase] at any stage of the 39ºC local heating protocol (main effects P ≥ 0.08). Conclusion: These data indicate there is no impact of biological sex on the vasodilatory response of the cutaneous vasculature to 39ºC local heating in young healthy adults when women are tested at random across the menstrual cycle. Funding: National Institutes of Health Grant T-32-5T32AG049676 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.