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 non-heat 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 sub-study (10 young adults, 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, twelve 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, while in the second bout, all sites were treated with either 1) a 5% DMSO (control), 2) 100μM HC030031, 3) 20 mM L-NAME, a non-selective 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.