Sex differences in sympathetic neurovascular transduction of action potential discharge during fatiguing handgrip exercise in young adults
Authors: D'Souza Andrew , Manabe Kazumasa , Hissen Sarah , Coombs Geoff , Washio Takuro , Annis Meghan , Sanchez Belinda , Fu Qi , Shoemaker Kevin 
Published: May 2023

Males, and females using oral contraception (OC), exhibit larger increases in muscle sympathetic nerve activity (MSNA) during exercise than naturally menstruating females. Furthermore, sympathetic transduction into blood pressure during exercise is greater in females using OC than naturally menstruating females. Though limb vasoconstriction for a given dose of norepinephrine is blunted in females (via estrogen mediated β-adrenergic vasodilation) compared to males at rest, the impact of sex, menstrual cycle, and OC on MSNA and action potential (AP) discharge, as well as sympathetic neurovascular transduction (sNVT) during exercise remains unknown. We hypothesized that during exercise: 1) males would exhibit the largest increases in MSNA and AP recruitment as well as sNVT, and 2) naturally menstruating females would exhibit less sympathetic reactivity and sNVT compared to females using OC. MSNA, AP discharge (microneurography and a continuous wavelet transform), and leg blood flow (doppler ultrasound) were assessed in 10 naturally menstruating females (25±4 years (mean±SD)), 7 females using OC (26±5 years), and 6 males (YM; 26±5 years) during static handgrip exercise (SHG) to fatigue at 40% of maximal voluntary contraction force. SHG duration was divided into four equal stages. Leg vascular conductance (LVC) was calculated as leg blood flow divided by mean arterial pressure, and sNVT was quantified as the slope of the relationship between changes in (Δ) LVC and MSNA or AP discharge. Females were tested in the mid luteal (ML) and active pill OC phases. Linear mixed-model analyses were used to assess ΔMSNA, AP discharge, and LVC during SHG, whereas sNVT was assessed via one-way ANOVAs. No group differences were observed for ΔMSNA burst frequency ( P=0.937), incidence ( P=0.928), amplitude ( P=0.293) or total activity ( P=0.966) throughout exercise. Similarly, ΔAPs/burst ( P=0.59), ΔClusters/burst ( P=0.393), ΔTotal clusters ( P=0.639) were not different between groups throughout exercise. Conversely, an interaction effect was observed for ΔLVC during exercise ( P=0.004), with ML females tending to have smaller ΔLVC than YM at 25% ( P=0.132), 75% ( P=0.174) and 100% ( P=0.103) of SHG. Thus, sNVT of MSNA burst amplitude (ML: -0.007±0.007, YM: -0.023±0.01 Δml/min/ΔAU; post-hoc P=0.008), total activity (ML: -0.00007±0.00007, YM: -0.0003±0.0001 Δml/min/ΔAU/min-1; post-hoc P=0.002), and total AP clusters (ML: -0.03±0.03, YM: -0.08±0.03 Δml/min/Δclusters; post-hoc P=0.027) was lower in ML females relative to YM. In females using OC, sNVT was not different compared to ML females or YM (all post-hoc P>0.05 ). sNVT of other MSNA/AP indices were not different between groups (all P>0.05). These preliminary data indicate that sNVT of MSNA burst amplitude and total AP clusters is greater in males than naturally menstruating females, and that OC use does not impact AP discharge or sNVT within females during static handgrip exercise. Supported by the Natural Sciences and Engineering Council of Canada 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.