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Objectives Heat shock protein 90 (HSP90) contributes to cutaneous vasodilatation during exercise in the heat through nitric oxide (NO) synthase (NOS)–dependent mechanisms in young adults. We hypothesized that similar responses would be observed in older middle‐aged adults. Methods In nineteen habitually active older middle‐aged (56 ± 5 years) men (n = 9) and women (n = 10), cutaneous vascular conductance (CVC) was measured at four forearm skin sites continuously treated with (a) lactated Ringers solution (Control), (b) 10 mmol/L L‐NAME (NOS inhibitor), (c) 178 μmol/L geldanamycin (HSP90 inhibitor), or (d) 10 mmol/L L‐NAME and 178 μmol/L geldanamycin combined. Participants rested in an upright semi‐recumbent position in the heat (35°C) for 70 minutes, followed by a 50‐minute bout of moderate‐intensity cycling (~55% peak oxygen uptake) and a 30‐minute recovery period in the heat. Results In both men and women, we observed no significant effects of HSP90 inhibition on CVC throughout rest, exercise, and recovery in the heat (all P > 0.27). Conversely, NOS inhibition and dual NOS and HSP90 inhibition attenuated CVC relative to Control throughout the protocol (all P ≤ 0.05). Conclusions While NOS mediates cutaneous vasodilatation during rest, exercise, and recovery in the heat, HSP90 does not measurably influence this response in habitually active older middle‐aged men or women under these conditions.

Regional variations in cutaneous vasodilatation and sweating exist across the body. Nitric oxide (NO) is an important modulator of these heat loss responses in the forearm. However, whether regional differences in NO-dependent cutaneous vasodilatation and sweating exist remain uncertain. In 14 habitually active young men (23 ± 4 years of age), cutaneous vascular conductance (CVC %max ) and local sweat rates were assessed at six skin sites. On each of the dorsal forearm, chest and upper back (trapezius), sites were continuously perfused with either lactated Ringer solution (control) or 10 mM N -nitro-L-arginine (L-NNA; an NO synthase inhibitor) dissolved in Ringer solution, via microdialysis. At all sites, cutaneous vasodilatation and sweating were induced by co-administration of the cholinergic agonist methacholine (1, 10, 100, 1000 and 2000 mM;25 min per dose) followed by 50 mM sodium nitroprusside (20-25 min) to induce maximal vasodilatation. The L-NNA attenuated CVC %max relative to the control conditions for all regions (all P < 0.05), and NO-dependent vasodilatation was greater at the forearm compared with the back and chest (both P < 0.05). Furthermore, maximal vasodilatation was higher at the back and chest relative to the forearm (both P < 0.05). Conversely, L-NNA had negligible effects on sweating across the body (all P > 0.05). Peak local sweat rate was higher at the back relative to the forearm (P < 0.05), with a similar trend observed for the chest. In habitually active young men, NOdependent cholinergic cutaneous vasodilatation varied across the body, and the contribution to cholinergic sweating was negligible. These findings advance our understanding of the mechanisms influencing regional variations in cutaneous vasodilatation and sweating during pharmacological stimulation. K E Y W O R D Sacetylcholine, heat loss, microdialysis, muscarinic receptors, thermoregulation 1 wileyonlinelibrary.com/journal/eph Experimental Physiology. 2020;105:236-243.