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.

In humans, exercise-induced plasma volume (PV) expansion is typically associated with an increase in plasma albumin content, due in part to an increase in hepatic albumin synthesis. We tested the ability of a 12-day high-intensity intermittent exercise protocol to induce an increase in PV in rodents. Since albumin synthesis is transcriptionally regulated, we tested the hypothesis that exercise training would induce an increase in hepatic albumin gene expression. Fifty adult male Sprague-Dawley rats weighing between 245 and 350 g were randomly assigned to one of five groups: cage control (CC), sham exercise (sham), continuous moderate-intensity exercise training (MI), high-intensity intermittent exercise training (HI), or a single day of HI training (1-HI). Twenty-four hours after the last training session, rats were anesthetized. PV was determined, and the liver was removed, flash frozen, and stored for later analysis. Citrate synthase (CS) activity of the red quadriceps muscle, a marker of aerobic adaptation, increased with training (MI and HI) and in response to 1-HI (P < 0.05). We did not see a significant exercise-induced PV expansion as PV averaged 23.6 +/- 2.7 ml/kg body wt in the CC group and 26.6 +/- 1.3 ml/kg body wt in the HI group (P > 0.05). However, hepatic albumin mRNA expression, as determined by real-time PCR, increased 2.9 +/- 0.4- and 4.1 +/- 0.4-fold after MI and HI, respectively, compared with CC. A single bout of HI (1-HI) did not alter hepatic albumin mRNA expression. These data demonstrate an increase in both CS activity and hepatic albumin gene expression with 12 days of aerobic exercise training in the rodent with a rapid (within 24 h) adaptation in the skeletal muscle to high-intensity intermittent exercise.

We tested the hypothesis that cutaneous vasodilation during local skin heating in humans could be manipulated based upon the ability to desensitize TRPV4 ion channels by applying the thermal stimuli in a series of pulses. Each subject was instrumented with intradermal microdialysis probes in the dorsal forearm skin and perfused with 0.9% saline at 1.5 μl/min with local skin temperature controlled with a Peltier unit (9 cm2) at 34°C. Local skin temperature was manipulated for 50 min in two classic ways: a step increase to 38°C (0.1°C/s, n = 10), and a step increase to 42°C (n = 10). To desensitize TRPV4 ion channels local skin temperature was manipulated in the following way: pulsed increase to 38°C (1 pulse per min, 30 s duration, 1.0°C/s, n = 10), and 4) pulsed increase to 42°C (1.0°C/s, n = 9). Skin blood flow (SkBF, laser Doppler) was recorded directly over the middle microdialysis probe and the dialysate from all three probes were collected during baseline (34°C) and each skin heating period. The overall cutaneous vascular conductance (CVC) response to local heating was estimated from the area under the % CVCmax-time curve. The appearance of the neuropeptide calcitonin gene related peptide (CGRP) in dialysate did not change with skin heating in any protocol. For the skin temperature challenge of 34 to 38°C, the area under the % CVCmax-time curve averaged 1196 ± 295 (SD) % CVCmax•min, which was larger than the 656 ± 282% CVCmax•min during pulsed heating (p < 0.05). For the skin temperature challenge of 34 to 42°C, the area under the % CVCmax-time curve averaged 2678 ± 458% CVCmax•min, which was larger than the 1954 ± 533% CVCmax•min during pulsed heating (p < 0.05). The area under the % CVCmax•min curve, was directly proportional to the accumulated local skin thermal stress (in °C•min) (r2 = 0.62, p < 0.05, n = 39). This association indicates a critical role of local integration of thermosensitive receptors in mediating the cutaneous vasodilator response to local skin heating. Given that we saw no differences in the levels of CGRP in dialysate, the role of the vasoactive peptide CGRP in the cutaneous vasodilator response to local skin heating is not supported by our data.

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