Nitric oxide and cutaneous active vasodilation during heat stress in humans

Abstract

Whether nitric oxide (NO) is involved in cutaneous active vasodilation during hyperthermia in humans is unclear. We tested for a role of NO in this process during heat stress (water-perfused suits) in seven healthy subjects. Two forearm sites were instrumented with intradermal microdialysis probes. One site was perfused with the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) dissolved in Ringer solution to abolish NO production. The other site was perfused with Ringer solution only. At those sites, skin blood flow (laser-Doppler flowmetry) and sweat rate were simultaneously and continuously monitored. Cutaneous vascular conductance, calculated from laser-Doppler flowmetry and mean arterial pressure, was normalized to maximal levels as achieved by perfusion with the NO donor nitroprusside through the microdialysis probes. Under normothermic conditions, L-NAME did not significantly reduce cutaneous vascular conductance. During hyperthermia, with skin temperature held at 38-38.5 degreesC, internal temperature rose from 36.66 +/- 0.10 to 37.34 +/- 0.06 degreesC (P < 0.01). Cutaneous vascular conductance at untreated sites increased from 12 +/- 2 to 44 +/- 5% of maximum, but only rose from 13 +/- 2 to 30 +/- 5% of maximum at L-NAME-treated sites (P < 0.05 between sites) during heat stress. L-NAME had no effect on sweat rate (P > 0.05). Thus cutaneous active vasodilation requires functional NO synthase to achieve full expression.

Thermoregulation in hypertensive men exercising in the heat with water ingestion

“…These thermoregulatory results suggest skin vasodilation related to water ingestion. It is known that during exercise the sweating rate is increased through a sympathetic cholinergic pathway and that the nervous stimulation of sweat glands produces some vasoactive substances, which, in turn, cause skin vasodilation (7,25). In the present study, the sweating rate of hypertensive was similar to the sweating rate of normal subjects, which is not consistent with the supposed higher sympathetic cholinergic sweat gland stimulation-related vasodilation in hypertensive subjects.…”

Noninvasive interrogation of microvasculature for signs of endothelial dysfunction in patients with chronic renal failure

“…1. Kellogg and colleagues (16) first showed and Minson (25) corroborated that the dilator response to local heating is related to NO, which plays a major role in the sustained cutaneous vasodilation (i.e., the secondary plateau) of prolonged heating. The first peak is blunted by NO synthase inhibitors, but the second peak and plateau are more markedly reduced.…”

“…Local heating of nonglabrous skin such as the forearm evokes vasodilation that is mediated by neurogenic reflexes and locally produced endothelium-dependent vasodilatory substances (12,16,25,18). The LDPM probe was heated to 43°C over a 2-min period.…”

Ischaemic preconditioning does not alter the determinants of endurance running performance in the heat

“…Adenosine accumulation has also been suggested to maintain endothelium function, when it is normally impaired following strenuous exercise (Bailey, Birk, et al 2012). Alongside adenosine, ischaemia stimulates increased endothelial nitric oxide (NO) release that attenuates sympathetic vasoconstriction, inducing smooth muscle relaxation as part of the secondary plateau phase of the bimodal cutaneous response to local hyperthermia (Kellogg et al 1998). It is possible that under heat stress, any reduction in skeletal muscle energy consumption were too small for these measures to detect or, from a haemodynamic perspective, skeletal muscle may not be sensitive to further increases in NO following IP, due to the apparently greater role of prostaglandins, relative to NO for inducing vasodilation (Kellogg et al 2005).…”