The role of estradiol on sensory nerve-mediated dilation in postmenopausal women

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BACKGROUND: Local heating of the skin elicits a biphasic vasodilatory response. The initial peak of this response is largely mediated by sensory nerve mechanisms. Receptors for estradiol (E2), the primary form of estrogen, have been found on peripheral sensory neurons indicating E2 impacts the nociceptive response. In animal models, E2 may decrease pain tolerance or act as an analgesic but it is currently unclear how E2 affects sensory nerve-mediated responses in women, particularly in E2-deficient postmenopausal women. PURPOSE: We tested the hypothesis that E2 augments sensory nerve-mediated vasodilation during local heating in E2-deficient postmenopausal women. METHODS: We measured cutaneous vasodilation to local heating (42°C) via laser Doppler flowmetry during microdialysis perfusions of lactated Ringer’s (control) and in a subset (n=4), L-NAME (non-selective nitric oxide synthase inhibition; 15mM) in 10 healthy postmenopausal women (55±2 yrs) at baseline (BL) and after 7 days E2 administration using a transdermal patch (E2; 0.1 mg/day, Vivelle-Dot). Cutaneous vascular conductance (CVC) was calculated as SkBF/MAP normalized to maximal vasodilation achieved by perfusion of sodium nitroprusside (28mM) and heating to 43°C. RESULTS: All women were less than 10 years post menopause (average 5±3 years), normotensive (SBP: 123±12 mmHg; DBP 77±5 mmHg) and not obese (BMI: 24±3 kg/m2). Sensory nerve-mediated dilation was unaffected by E2 administration (E2: 56±8 vs BL: 55±13 %CVCmax; p=0.72). Inhibition of eNOS with L-NAME did not blunt sensory nerve-mediated dilation and was not impacted by E2 (E2: 71±18 vs BL: 56±33 %CVCmax; p=0.55). In a subset (n=5) serum E2 concentration increased after E2 administration (E2: 80.42±11.90 vs BL: 25.74±4.42; p=0.0005) CONCLUSIONS: These preliminary findings suggest E2 administration does not impact sensory nerve-mediated dilation in postmenopausal women. Furthermore, sensory nerve-mediated dilation does not appear to be mediated by nitric oxide. Additional research is needed to further understand the impact of sex hormones and aging on sensory nerve-mediated dilation in women. Research supported by AHA award 16SDG30700015 and NIH Grant P20 GM113125 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.