Nonselective NOS inhibition blunts the sweat response to exercise in a warm environment

Abstract

The role of nitric oxide synthase (NOS) inhibition in modulating human thermoregulatory control of sweating and cutaneous dilation was examined in 10 subjects (5 men and 5 women). Three intradermal microdialysis probes were placed in nonglabrous skin of the dorsum of the forearm. The control site was perfused with 0.9% saline, while the two remaining sites were perfused with a nonselective NOS inhibitor: 10 mM N(G)-nitro-L-arginine (L-NAME) or 10 mM N(G)-monomethyl-L-arginine (L-NMMA). Local sweat rate (SR) and skin blood flow (laser-Doppler velocimetry) were monitored directly over the path of the intradermal microdialysis probe while arterial blood pressure was measured in the opposite arm noninvasively. Thermoregulatory responses were induced by cycle ergometer exercise (60% peak oxygen consumption) in a warm environment (30 degrees C). Esophageal temperature increased 1.5 +/- 0.2 degrees C during the 30 min of exercise. The cutaneous dilator response between 5 and 30 min of exercise in the heat was attenuated by both 10 mM L-NAME and 10 mM L-NMMA (P < 0.05). However, 10 mM L-NAME was more effective in blunting the rise in cutaneous vascular conductance during exercise than L-NMMA (P < 0.05). NOS inhibition also reduced the rise in local SR between 10 and 30 min of exercise (P < 0.05). In this case, 10 mM L-NMMA was more effective in limiting the increase in local SR than 10 mM L-NAME (P < 0.05). We conclude that local production of nitric oxide in the skin or around the sweat gland augments local SR and cutaneous dilation during exercise in the heat.

Fig. 1.

Influence of 10 mM N^G-nitro-l-arginine (l-NAME) and 10 mM N^G-monomethyl-l-arginine (l-NMMA) on the skin blood flow (expressed as a % of maximum) response to 40 min of local heating. Values are means ± SE for 10 subjects in each group. Trauma represents the skin blood flow response within the first 3–5 min following guide needle insertion and placement of the intradermal microdialysis probe. NOS, nitric oxide synthase. Skin blood flow for the saline control group was significantly higher than l-NAME or l-NMMA from 4 min through 40 min, P < 0.05.

Fig. 2.

Body temperature responses to 30 min of cycle ergometer exercise (60% peak oxygen consumption) at an ambient temperature of 30°C in control (saline) and NOS-inhibited (l-NAME and l-NMMA) skin sites. Values are means ± SE for 10 subjects during 0 to 20 min of exercise, 9 subjects from 21 to 27 min of exercise, and 8 subjects from 28 to 30 min of exercise. T_es, esophageal temperature; T_skin, mean skin temperature; T_forearm, local forearm temperature. †P < 0.05 different from time 0.

Fig. 3.

Cutaneous vascular conductance (CVC) response to thirty min of cycle ergometer exercise (60% peak oxygen consumption) at an ambient temperature of 30°C in control (saline) and NOS-inhibited (l-NAME and l-NMMA) skin sites. Values are means ± SE for 10 subjects during 0 to 20 min of exercise, 9 subjects from 21 to 27 min of exercise, and 8 subjects from 28 to 30 min of exercise.

Fig. 4.

Local sweat rate response to 30 min of cycle ergometer exercise (60% oxygen consumption) at an ambient temperature of 30°C in control (saline) and NOS-inhibited (l-NAME and l-NMMA) skin sites. Values are means ± SE for 10 subjects during 0 to 20 min of exercise, 9 subjects from 21 to 27 min of exercise, and 8 subjects from 28 to 30 min of exercise.

Fig. 5.

Pattern of sweat gland recruitment during thermoregulatory sweating induced by exercise in a warm (30°C) environment at saline-treated and l-NMMA-treated skin sites. The image represents a representative pattern of sweat gland activation for a single subject during the first 10 min of exercise.