Hypoxic vasodilation in pre- and perimenopausal females: role of β-adrenergic receptors

Introduction: Hypoxia elicits peripheral vasodilation, which is lower in post-menopausal compared with pre-menopausal females. Whether impairments in hypoxic vasodilation occur earlier in the menopause transition (i.e., perimenopause) are unknown, and contributing mechanisms are not well defined. Given β-adrenergic receptors (β-ARs) mediate a portion of hypoxic vasodilation, we hypothesized: 1) hypoxic vasodilation would be lower in peri- vs pre-menopausal females and 2) β-AR blockade would blunt hypoxic vasodilation, with greater effects in pre- vs perimenopausal participants. Methods: Fifteen premenopausal (27±8 yr, 24±3 kg/m 2 , early follicular phase) and 5 perimenopausal (47±3 yr, 24±3 kg/m 2 ) females completed two study visits randomized and blinded to oral placebo or propranolol (β-AR antagonist, 1 mg/kg). Forearm blood flow (FBF, venous occlusion plethysmography) and blood pressure (BP, finger photoplethysmography) were assessed during a 10-min normoxic baseline, followed by 5-min of steady-state hypoxia (80-85% SpO2). FBF was normalized for mean BP (forearm vascular conductance, FVC) and a change (Δ) in FVC from baseline was calculated as an index of hypoxic vasodilation. Results: Steady-state hypoxia elicited vasodilation in premenopausal females (main effect of hypoxia, p=0.008), while FVC remained unchanged during hypoxia in perimenopausal females (main effect of hypoxia, p=0.691). The resultant change in FVC with hypoxia was lower in peri- vs premenopausal females (ΔFVC: 0.076±0.173 vs 2.038±2.692 mL/dL/100 mmHg, p=0.023). Propranolol lowered FVC in premenopausal females (main effect of propranolol, p=0.014) but had no effect in perimenopausal females (main effect of propranolol, p=0.719). Under propranolol, the change in FVC with hypoxia remained lower in perimenopausal vs premenopausal females (ΔFVC: 0.011 ± 0.414 vs 1.003 ± 0.822 mL/dL/100 mmHg; p=0.0198). Conclusion: These preliminary data support impaired hypoxic vasodilation in perimenopausal females. Group differences in hypoxic vasodilation persist during β-AR blockade, supporting mechanisms beyond β-AR signaling likely contribute to impaired vasodilatory responses during the menopause transition. Future work should examine receptor-specific mechanisms and explore pharmacologic strategies to restore vasodilatory responsiveness to hypoxia. Funding: AHA 909014 (DWJ), HL153523 (JKL), University of Missouri Research Council (NGB, BPB, JKL), APS SURF (VLDV) This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.