Involvement of nitric oxide synthase and reactive oxygen species in TRPA1-mediated cutaneous vasodilation in young and older adults.

Abstract

To investigate the nitric oxide synthase (NOS) and reactive oxygen species (ROS) contributions of the cutaneous vasodilator response to transient receptor potential ankyrin-1 channel (TRPA1) activation in young and older adults. In sixteen young (20±2years, 8 females) and sixteen older adults (61±5years, 8 females), cutaneous vascular conductance normalized to maximum vasodilation (%CVCmax) was assessed at four dorsal forearm skin sites continuously perfused via microdialysis with: 1) vehicle solution (Control, 2% dimethyl sulfoxide, 2% Ringer, 96% propylene glycol), 2) 10mM Ascorbate (non-specific ROS inhibitor), 3) 10mML-NAME (non-specific NOS inhibitor), or 4) Ascorbate+L-NAME. The TRPA1 agonist cinnamaldehyde was co-administered at all sites [0% (baseline), 2.9%, 8.8%, 26.4%; ≥ 30min per dose]. %CVCmax was not different between groups for Control, L-NAME, and Ascorbate (all p>0.05). However, there were significant main dose effects for each site wherein %CVCmax was greater than baseline from 2.9% to 26.4% cinnamaldehyde for Control and Ascorbate, and at 26.4% cinnamaldehyde for L-NAME and Ascorbate+L-NAME (all p<0.05). For Ascorbate+L-NAME, there was a significant main group effect, wherein perfusion was 6 %CVCmax [95% CI: 2, 11, p<0.05] greater in the older compared to the young group across all cinnamaldehyde doses. There was a significant main site effect for area under the curve wherein L-NAME and Ascorbate+L-NAME were lower than Control and Ascorbate across groups (all p<0.05). The NOS-dependent cutaneous vasodilator response to TRPA1 activation is maintained in older adults, with no detectable contribution of ascorbate-sensitive ROS in either age group.