β-Adrenergic receptors mediate sex differences in vasodilation but not sympathetic-mediated vasoconstriction during hypoxia.

β-Adrenergic receptors (ARs) mediate a portion of hypoxic vasodilation and blunt sympathetic vasoconstriction at rest. Vascular β-AR sensitivity may be greater in females relative to males; however, their sex-specific role during hypoxia has yet to be examined. We hypothesized β-AR blockade would blunt hypoxic vasodilation and augment sympathetic vasoconstriction during hypoxia, with effects greater in females relative to males. Ten female (26 ± 8 yr, 23 ± 3 kg/m2) and 13 male (28 ± 7 yr, 25 ± 2 kg/m2) adults completed two study visits randomized and blinded to oral placebo or propranolol (β-AR blockade; 1 mg/kg) (NCT05256069). Forearm blood flow (FBF, venous occlusion plethysmography) and blood pressure (BP, finger photoplethysmography) were assessed for 10-min normoxic rest, followed by 5 min of steady-state hypoxia (∼80% [Formula: see text]). Sympathetic activation was achieved via a cold pressor test (CPT) conducted during normoxia and steady-state hypoxia. FBF was normalized for mean BP (forearm vascular conductance, FVC). Absolute (Δ) and relative (%) changes in FVC in response to hypoxia and CPT were calculated. β-AR blockade significantly reduced hypoxic vasodilation in females but not in males (interaction of hypoxia and sex: ΔFVC P = 0.029, %FVC P = 0.030). Sympathetic vasoconstriction was attenuated during hypoxia in females compared with males (main effect of sex: ΔFVC P = 0.005, %FVC P = 0.015), but there was no effect of β-AR blockade in either sex (main effect of drug: ΔFVC P = 0.406; %FVC P = 0.238; interaction of drug and sex: ΔFVC P = 0.619, %FVC P = 0.390). β-Adrenergic receptors mediate hypoxic dilation in females but not in males and do not restrain sympathetic-mediated vasoconstriction during hypoxia in either sex.NEW & NOTEWORTHY β-Adrenergic receptors contribute to hypoxic vasodilation, attenuate sympathetic vasoconstriction at rest, and are more sensitive in females versus males. We hypothesized β-adrenergic receptor blockade would blunt hypoxic vasodilation and augment the sympathetic vasoconstriction during hypoxia, with effects greater in females relative to males. Present data demonstrate β-adrenergic receptors contribute to hypoxic vasodilation in females but do not restrain sympathetic-mediated vasoconstriction during hypoxia in either sex.