TRPA1 channels modulate cutaneous vasodilation during exercise in the heat in young adults when NOS is inhibited.

Abstract

Nitric oxide synthase (NOS) is an important mediator of cutaneous vasodilation during exercise-heat stress. We recently reported that pharmacological activation of transient receptor potential ankyrin 1 (TRPA1) channel mediates cutaneous vasodilation via NOS-dependent mechanisms under nonheat stress-resting conditions. Here, we hypothesized that TRPA1 channel activation would contribute to cutaneous vasodilation during exercise in the heat via NOS-dependent mechanisms. To assess this response, we first conducted TRPA1 channel antagonist verification substudy (10 young adults and 5 women) wherein 1 mM ASP7663 (TRPA1 channel agonist) increased cutaneous vascular conductance (CVC; cutaneous blood flow divided by mean arterial pressure) and this response was blocked by ∼50% with 100 μM HC030031, a known TRPA1 channel antagonist. Subsequently, 12 young adults (5 women) completed two bouts of 30-min moderate-intensity cycling (45% of their predetermined peak oxygen uptake) in the heat (35°C). During the first exercise, CVC was evaluated at four dorsal forearm skin sites perfused with a 5% DMSO, whereas in the second bout, all sites were treated with either 1) a 5% DMSO (control), 2) 100 µM HC030031, 3) 20 mM l-NAME, a nonselective NOS inhibitor, or 4) combination of both. No between-site differences in CVC were measured during the first exercise (P > 0.182). During the second exercise, HC030031 alone had no effect on CVC relative to the control (all P > 0.104). Both l-NAME and HC030031 + l-NAME reduced CVC (all P < 0.001), with the combined treatment showing a greater reduction (all P < 0.001). We showed that TRPA1 channels mediate cutaneous vasodilation during exercise-heat stress only when NOS is inhibited.NEW & NOTEWORTHY We demonstrated that the administration of TRPA1 channel antagonist HC030031 only appears to attenuate cutaneous vasodilation during exercise in the heat when nitric oxide synthase (NOS) is inhibited. TRPA1 channels may function as a "backup system" to maintain cutaneous vasodilation when NOS-dependent vasodilation is compromised during exercise in the heat.