Sex- and limb-specific differences in the nitric oxide-dependent cutaneous vasodilation in response to local heating

Local heating of the skin is commonly used to assess cutaneous microvasculature function. Controversy exists as to whether there are limb or sex differences in the nitric oxide (NO)-dependent contribution to this vasodilation, as well as the NO synthase (NOS) isoform mediating the responses. We tested the hypotheses that 1) NO-dependent vasodilation would be greater in the calf compared with the forearm; 2) total NO-dependent dilation would not be different between sexes within limb; and 3) women would exhibit greater neuronal NOS (nNOS)-dependent vasodilation in the calf. Two microdialysis fibers were placed in the skin of the ventral forearm and the calf of 19 (10 male and 9 female) young (23 ± 1 yr) adults for the local delivery of Ringer solution (control) or 5 mM N(ω)-propyl-l-arginine (NPLA; nNOS inhibition). Vasodilation was induced by local heating (42°C) at each site, after which 20 mM N(G)-nitro-l-arginine methyl ester (l-NAME) was perfused for within-site assessment of NO-dependent vasodilation. Cutaneous vascular conductance (CVC) was calculated as laser-Doppler flux/mean arterial pressure and normalized to maximum (28 mM sodium nitroprusside, 43°C). Total NO-dependent vasodilation in the calf was lower compared with the forearm in both sexes (Ringer: 42 ± 5 vs. 62 ± 4%; P < 0.05; NPLA: 37 ± 3 vs. 59 ± 5%; P < 0.05) and total NO-dependent vasodilation was lower in the forearm for women (Ringer: 52 ± 6 vs. 71 ± 4%; P < 0.05; NPLA: 47 ± 6 vs. 68 ± 5%; P < 0.05). NPLA did not affect total or NO-dependent vasodilation across limbs in either sex (P > 0.05). These data suggest that the NO-dependent component of local heating-induced cutaneous vasodilation is lower in the calf compared with the forearm. Contrary to our original hypothesis, there was no contribution of nNOS to NO-dependent vasodilation in either limb during local heating.