Effects of L-type voltage-gated Ca2+ channel blockade on cholinergic and thermal sweating in habitually trained and untrained men.

We evaluated the hypothesis that the activation of L-type voltage-gated Ca2+ channels contributes to exercise training-induced augmentation in cholinergic sweating. On separate days, 10 habitually trained and 10 untrained men participated in two experimental protocols. Prior to each protocol, we administered 1% verapamil (Verapamil, L-type voltage-gated Ca2+ channel blocker) and saline (Control) at forearm skin sites on both arms via transdermal iontophoresis. In protocol 1, we administered low (0.001%) and high (1%) doses of pilocarpine at both the verapamil-treated and verapamil-untreated forearm sites. In protocol 2, participants were passively heated by immersing their limbs in hot water (43°C) until rectal temperature increased by 1.0°C above baseline resting levels. Sweat rate at all forearm sites was continuously measured throughout both protocols. Pilocarpine-induced sweating in Control was higher in trained than in untrained men for both the concentrations of pilocarpine (both P ≤ 0.001). Pilocarpine-induced sweating at the low-dose site was attenuated at the Verapamil versus the Control site in both the groups (both P ≤ 0.004), albeit the reduction was greater in trained as compared with in untrained men (P = 0.005). The verapamil-mediated reduction in sweating remained intact at the high-dose pilocarpine site in the untrained men (P = 0.004) but not the trained men (P = 0.180). Sweating did not differ between Control and Verapamil sites with increases in rectal temperature in both groups (interaction, P = 0.571). We show that activation of L-type voltage-gated Ca2+ channels modulates sweat production in habitually trained men induced by a low dose of pilocarpine. However, no effect on sweating was observed during passive heating in either group.

Respiratory mechanics and cerebral blood flow during heat-induced hyperventilation and its voluntary suppression in passively heated humans.

We investigated whether heat-induced hyperventilation can be voluntarily prevented, and, if so, how this modulates respiratory mechanics and cerebral blood flow in resting heated humans. In two separate trials, 10 healthy men were passively heated using lower body hot-water immersion and a water-perfused garment covering their upper body (both 41°C) until esophageal temperature (Tes ) reached 39°C or volitional termination. In each trial, participants breathed normally (normal-breathing) or voluntarily controlled minute ventilation (VE ) at a level equivalent to that observed after 5 min of heating (controlled-breathing). Respiratory gases, middle cerebral artery blood velocity (MCAV), work of breathing, and end-expiratory and inspiratory lung volumes were measured. During normal-breathing, VE increased as Tes rose above 38.0 ± 0.3°C, whereas controlled-breathing diminished the increase in VE (VE at Tes  = 38.6°C: 25.6 ± 5.9 and 11.9 ± 1.3 L min-1 during normal- and controlled-breathing, respectively, P < 0.001). During normal-breathing, end-tidal CO2 pressure and MCAV decreased with rising Tes , but controlled-breathing diminished these reductions (at Tes  = 38.6°C, 24.7 ± 5.0 vs. 39.5 ± 2.8 mmHg; 44.9 ± 5.9 vs. 60.2 ± 6.3 cm sec-1 , both P < 0.001). The work of breathing correlated positively with changes in VE (P < 0.001) and was lower during controlled- than normal-breathing (16.1 ± 12.6 and 59.4 ± 49.5 J min-1 , respectively, at heating termination, P = 0.013). End-expiratory and inspiratory lung volumes did not differ between trials (P = 0.25 and 0.71, respectively). These results suggest that during passive heating at rest, heat-induced hyperventilation increases the work of breathing without affecting end-expiratory lung volume, and that voluntary control of breathing can nearly abolish this hyperventilation, thereby diminishing hypocapnia, cerebral hypoperfusion, and increased work of breathing.

Influence of dietary nitrate supplementation on local sweating and cutaneous vascular responses during exercise in a hot environment.

PURPOSE: We investigated the influence of inorganic nitrate ([Formula: see text]) supplementation on local sweating and cutaneous vascular responses during exercise in hot conditions. METHOD: Eight healthy, young subjects were assigned in a randomized, double-blind, crossover design to receive [Formula: see text]-rich beetroot (BR) juice (140 mL/day, containing ~ 8 mmol of [Formula: see text]) and [Formula: see text]-depleted placebo (PL) juice (140 mL/day, containing ~ 0.003 mmol of [Formula: see text]) for 3 days. On day 3 of supplementation, subjects cycled at an intensity corresponding to 55% of [Formula: see text]O2max for 30 min in hot conditions (30 °C, 50% relative humidity). Chest and forearm sweat rate (SR) and skin blood flow (SkBF), were measured continuously. Cutaneous vascular conductance (CVC) was calculated by SkBF/mean arterial pressure (MAP). RESULTS: Prior to exercise, plasma [Formula: see text] (21 ± 6 and 581 ± 161 µM) and nitrite ([Formula: see text], 87 ± 28 and 336 ± 156 nM) concentrations were higher after BR compared to PL supplementation (P ≤ 0.011, n = 6). Oesophageal, mean skin, and mean body temperatures during exercise were not different between conditions. In addition, BR supplementation did not affect SR, SkBF, and CVC during exercise. A lower MAP was found after 30 min of exercise following BR supplementation (112 ± 6 and 103 ± 6 mmHg for PL and BR, respectively, P = 0.021). CONCLUSION: These results suggest that inorganic [Formula: see text] supplementation, which increases the potential for O2-independent NO production, does not affect local sweating and cutaneous vascular responses, but attenuates blood pressure in young healthy subjects exercising in a hot environment.

Effect of hypocapnia on the sensitivity of hyperthermic hyperventilation and the cerebrovascular response in resting heated humans.

Elevating core temperature at rest causes increases in minute ventilation (V̇e), which lead to reductions in both arterial CO2 partial pressure (hypocapnia) and cerebral blood flow. We tested the hypothesis that in resting heated humans this hypocapnia diminishes the ventilatory sensitivity to rising core temperature but does not explain a large portion of the decrease in cerebral blood flow. Fourteen healthy men were passively heated using hot-water immersion (41°C) combined with a water-perfused suit, which caused esophageal temperature (Tes) to reach 39°C. During heating in two separate trials, end-tidal CO2 partial pressure decreased from the level before heating (39.4 ± 2.0 mmHg) to the end of heating (30.5 ± 6.3 mmHg) ( P = 0.005) in the Control trial. This decrease was prevented by breathing CO2-enriched air throughout the heating such that end-tidal CO2 partial pressure did not differ between the beginning (39.8 ± 1.5 mmHg) and end (40.9 ± 2.7 mmHg) of heating ( P = 1.00). The sensitivity to rising Tes (i.e., slope of the Tes - V̇E relation) did not differ between the Control and CO2-breathing trials (37.1 ± 43.1 vs. 16.5 ± 11.1 l·min-1·°C-1, P = 0.31). In both trials, middle cerebral artery blood velocity (MCAV) decreased early during heating (all P < 0.01), despite the absence of hyperventilation-induced hypocapnia. CO2 breathing increased MCAV relative to Control at the end of heating ( P = 0.005) and explained 36.6% of the heat-induced reduction in MCAV. These results indicate that during passive heating at rest ventilatory sensitivity to rising core temperature is not suppressed by hypocapnia and that most of the decrease in cerebral blood flow occurs independently of hypocapnia. NEW & NOTEWORTHY Hyperthermia causes hyperventilation and concomitant hypocapnia and cerebral hypoperfusion. The last may underlie central fatigue. We are the first to demonstrate that hyperthermia-induced hyperventilation is not suppressed by the resultant hypocapnia and that hypocapnia explains only 36% of cerebral hypoperfusion elicited by hyperthermia. These new findings advance our understanding of the mechanisms controlling ventilation and cerebral blood flow during heat stress, which may be useful for developing interventions aimed at preventing central fatigue during hyperthermia.

The effect of dietary nitrate supplementation on the spatial heterogeneity of quadriceps deoxygenation during heavy-intensity cycling.

This study investigated the influence of dietary inorganic nitrate (NO3-) supplementation on pulmonary O2 uptake (V˙O2) and muscle deoxyhemoglobin/myoglobin (i.e. deoxy [Hb + Mb]) kinetics during submaximal cycling exercise. In a randomized, placebo-controlled, cross-over study, eight healthy and physically active male subjects completed two step cycle tests at a work rate equivalent to 50% of the difference between the gas exchange threshold and peak V˙O2 over separate 4-day supplementation periods with NO3--rich (BR; providing 8.4 mmol NO3-∙day-1) and NO3--depleted (placebo; PLA) beetroot juice. Pulmonary V˙O2 was measured breath-by-breath and time-resolved near-infrared spectroscopy was utilized to quantify absolute deoxy [Hb + Mb] and total [Hb + Mb] within the rectus femoris, vastus lateralis, and vastus medialis There were no significant differences (P > 0.05) in the primary deoxy [Hb + Mb] mean response time or amplitude between the PLA and BR trials at each muscle site. BR significantly increased the mean (three-site) end-exercise deoxy [Hb + Mb] (PLA: 91 ± 9 vs. BR: 95 ± 12 µmol/L, P < 0.05), with a tendency to increase the mean (three-site) area under the curve for total [Hb + Mb] responses (PLA: 3650 ± 1188 vs. BR: 4467 ± 1315 µmol/L sec-1, P = 0.08). The V˙O2 slow component reduction after BR supplementation (PLA: 0.27 ± 0.07 vs. BR: 0.23 ± 0.08 L min-1, P = 0.07) correlated inversely with the mean increases in deoxy [Hb + Mb] and total [Hb + Mb] across the three muscle regions (r2 = 0.62 and 0.66, P < 0.05). Dietary NO3- supplementation increased O2 diffusive conductance across locomotor muscles in association with improved V˙O2 dynamics during heavy-intensity cycling transitions.

Time-of-day effect on nonthermal control of sweating response to maintained static exercise in humans.

To investigate the influence of nonthermal factors in the time-of-day effect on the sweating response to maintained static exercise, eight healthy male subjects performed handgrip exercise at 20%, 35% and 50% maximal voluntary contraction (MVC) for 60 s at 0600 hours (morning) and at 1800 hours (evening). Oesophageal temperature ( T(oes)) before the experiment showed a diurnal rhythm [mean (SEM)] [36.3 (0.1) (morning) compared to 36.8 (0.1) degrees C (evening), P<0.01]. Experiments were conducted with subjects in a state of mild hyperthermia during which the mean skin temperature ( T(sk)) was kept constant at 35.5-36.5 degrees C using a water-perfused suit to activate sudomotor responses. The T(oes) and mean T(sk)remained stable during the pre-exercise, handgrip exercise and recovery periods. The response in sweating rate (DeltaSR) on the chest and forearm to handgrip exercise increased significantly with increasing exercise intensity in both the morning and evening tests ( P<0.05). The DeltaSR on the palm did not change significantly with increasing exercise intensity in the morning test ( P>0.1). During handgrip exercise at 50% MVC only, DeltaSR on the chest, forearm and palm in the evening was significantly higher than in the morning ( P<0.05). On the other hand, mean arterial blood pressure and the rating of perceived exertion during 50% MVC handgrip exercise were not significantly different between the morning and evening ( P>0.1). These results indicate the presence of a time-of-day effect on nonthermal control of the sweating response to isometric handgrip exercise, and that this effect is dependent on exercise intensity.