Is nitric oxide involved in cutaneous vasodilation during body heating in humans?

The neurotransmitter responsible for neurogenic vasodilation in human skin during body heating is unknown. We sought to determine whether the vasodilating substance nitric oxide (NO) is involved in this phenomenon. Six subjects were heated for 50 min by use of a water-perfused suit while forearm blood flow (FBF) was measured with plethysmography and skin blood flow (SkBF) was measured by the laser-Doppler method in both arms. In one forearm, N(G)- monomethyl-L-arginine (L-NMMA), an NO synthase blocker, was infused into the brachial artery. Bolus doses of L-NMMA (≤4 mg/min) for 5 min were given to blunt NO-mediated vasodilator responses to acetylcholine (ACh, 64 μg/min). A continuous infusion of L-NMMA (≤1.0 mg/min) was used during body heating to maintain NO synthase blockade. In the forearm receiving L-NMMA, FBF was 1.8 ± 0.3 ml · 100 ml^-1 · min^-1 before drug infusion and rose to 9.5 ± 1.3 ml · 100 ml^-1 · min^-1 with ACh. After L-NMMA infusion, FBF was 1.3 ± 0.2 ml · 100 ml ^-1 · min^-1 and rose to 2.6 ± 0.4 ml · 100 ml^-1 · min^-1 with ACh (both P < 0.05 vs. pre-L-NMMA). Similar changes in SkBF were seen with ACh and L-NMMA, confirming that the drugs reached cutaneous vessels. With body heating, oral temperature increased by 1.2°C, heart rate increased by 34 beats/min, and mean arterial pressure remained constant at ~ 75 mmHg. FBF in the treated forearm rose to 11.5 ± 2.1 vs. 12.6 ± 1.7 ml · 100 ml^-1 · min^-1 in the control forearm (P > 0.05, control vs. treated response). These FBF responses were also similar to those in control studies without drug administration. SkBF responses to heating were also similar in both forearms. At the end of heating, variable dilator responses to repeat doses of ACh were observed. However, increases in blood flow with heating were similar bilaterally in the subjects whose dilator responses to ACh were blocked at the end of heating. These data suggest that NO does not play a major role in cutaneous vasodilation during body heating in humans.