Endothelial nitric oxide synthase control mechanisms in the cutaneous vasculature of humans in vivo

Nitric oxide (NO) participates in locally mediated vasodilation induced by increased local skin temperature (Tloc) and in sympathetically mediated vasodilation during whole body heat stress. We hypothesized that endothelial NOS (eNOS) participates in the former, but not the latter, response. We tested this hypothesis by examining the effects of the eNOS antagonist N-G-amino-L-arginine (L-NAA) on skin blood flow (SkBF) responses to increased Tloc and whole body heat stress. Microdialysis probes were inserted into forearm skin for drug delivery. One microdialysis site was perfused with L-NAA in Ringer solution and a second site with Ringer solution alone. SkBF [laser-Doppler flowmetry (LDF)] and blood pressure [mean arterial pressure (MAP)] were monitored, and cutaneous vascular conductance (CVC) was calculated (CVC = LDF divided by MAP). In protocol 1, Tloc was controlled with LDF/local heating units. Tloc initially was held at 34 degrees C and then increased to 41.5 degrees C. In protocol 2, after a normothermic period, whole body heat stress was induced (water-perfused suits). At the end of both protocols, 58 mM sodium nitroprusside was perfused at both microdialysis sites to cause maximal vasodilation for data normalization. In protocol 1, CVC at 34 degrees C Tloc did not differ between L-NAA-treated and untreated sites (P > 0.05). Local skin warming to 41.5 degrees C Tloc increased CVC at both sites. This response was attenuated at L-NAA-treated sites (P < 0.05). In protocol 2, during normothermia, CVC did not differ between L-NAA-treated and untreated sites (P > 0.05). During heat stress, CVC rose to similar levels at L-NAA-treated and untreated sites (P > 0.05). We conclude that eNOS is predominantly responsible for NO generation in skin during responses to increased Tloc, but not during reflex responses to whole body heat stress.