Effects of biological sex and oral contraception on the sympathetic neurocirculatory adjustments to static handgrip exercise in humans

While biological sex affects the neurocirculatory adjustments to exercise, the effects of sex hormones on sympathetic action potential (AP) patterns and ensuing vascular transduction remain unknown. We tested the hypothesis that males, and females using oral contraceptive pills (OCPs), would demonstrate larger increases in sympathetic activation and sympathetic vascular transduction compared with naturally menstruating females during static handgrip exercise (SHG) and postexercise circulatory occlusion (PECO). Young males [ n = 14, 25 (5) yr], females using OCPs [ n = 16, 24 (6) yr], and naturally menstruating females [ n = 18, 26 (4) yr] underwent assessments of multiunit muscle sympathetic nerve activity (MSNA)/AP discharge patterns (microneurography) and femoral artery blood flow (ultrasound) during fatiguing SHG at 40% maximum voluntary contraction and 2-min PECO. Sympathetic vascular transduction was determined as the quotient of the change in leg vascular conductance (LVC) and MSNA/AP discharge. Males demonstrated greater increases in APs/burst [males: Δ7 (6) vs. midluteal: Δ2 (3), P = 0.028] and total AP clusters [males: Δ5 (3) vs. midluteal: Δ2 (3), P = 0.008] compared with naturally menstruating females only but not those using OCPs during exercise (APs/burst: P = 0.171, total clusters: P = 0.455). Sympathetic vascular transduction of MSNA burst amplitude, APs/burst, and total AP clusters was greater in males and females using OCPs compared with naturally menstruating females (range: P = 0.004–0.044). In contrast, during PECO no group differences were observed in AP discharge (range: P = 0.510–0.872), and AP discharge was not related to LVC during PECO (range: P = 0.08–0.949). These data indicate that biological sex and OCP use impact the central generation of AP discharge, as well as the transduction of these neuronal messages into peripheral vasoconstriction during static exercise.