Introduction: The first-generation H1 antihistamine diphenhydramine hydrochloride (DPH) is a potent antimuscarinic agent which may compromise sweat output during heat stress. DPH consumption prior to exertional heat stress could further suppress the sweating response in females due to their lower postjunctional cholinergic sensitivity of the sweat glands relative to males. Objective and Hypothesis: The purpose of the present study was to test the hypothesis that DPH would reduce sweating to a greater extent in females relative to males due to differences in cholinergic sensitivity at the sweat gland. Methods: Equal groups (10 per group) of males (24±3 y; 82.6±10.1 kg; 182±5 cm) and females (22±3 y, 67.7±7.8 kg, 171±6 cm) completed two experimental trials presented in a randomized double-blind fashion. Upon arrival to lab, participants consumed either i) a placebo (PLA) pill or ii) 50 mg DPH and then rested in a room maintained at ~29.5°C & 35% RH for 2 hours before conducting a 60-minute treadmill march at a fixed rate of heat production relative to body surface area (~245 W/m2). Rectal temperature (Trec), local sweat rate of the forearm (LSR), and whole body sweat loss (WBSL) were measured. Sex-segregated analysis was conducted for each outcome variable as the difference between PLA and DPH. Results: Baseline Trec did not differ within sex between PLA and DPH (males: -0.10±0.26°C; females: -0.05±0.33°C, P=0.70), however a higher absolute baseline Trec was observed in females compared to males (P=0.006). In comparison to PLA, DPH did not exert a sex-dependent effect on ΔTrec following 60-min of exercise (males: 0.04±0.11°C; females: 0.02±0.37°C, P=0.90). No sex-dependent effect on the onset of sweating was observed between DPH and PLA (males: -0.4±2.6 min; females: 0.6±2.4 min, P=0.34). DPH did not exert a sex-dependent effect on LSR at steady-state (males: 0.03±0.25 mg/cm2/min; females: -0.01±0.21 mg/cm2/min, P=0.71). Lastly, no sex-dependent effect on WBSL was observed between PLA and DPH (males: 14±34 g; females: 6±43 g, P=0.98). Conclusion: Current evidence suggests that sex does not independently modulate the sweating response during exertional heat stress following the consumption of 50 mg of DPH. This research is supported by Dr. Ravanelli’s Research Seed Grant from the Centre for Research in Occupational Safety & Health, and Dr. Ravanelli’s Natural Sciences and Engineering Research Council of Canada Discovery Grant (PIN#2022-05096). This is the full abstract presented at the American Physiology Summit 2024 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.
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