No direct role for A1/A2 adenosine receptor activation to reflex cutaneous vasodilatation during whole-body heat stress in humans

Abstract

The precise mechanisms underlying reflex cutaneous vasodilatation during hyperthermia remain unresolved. The purpose of this study was to investigate a potential contribution of adenosine A1/A2 receptor activation to reflex cutaneous vasodilatation. Eight subjects were equipped with four microdialysis fibres on the left forearm, and each fibre was randomly assigned one of four treatments: (1) lactated Ringer's (control); (2) 4 mm of the non-selective A1/A2 adenosine receptor antagonist theophylline; (3) 10 mm L-NAME to inhibit nitric oxide (NO) synthase; and (4) combined 4 mm theophylline and 10 mm L-NAME. Laser-Doppler flowmetry (LDF) was used as an index of skin blood flow, and blood pressure was measured beat-by-beat via photoplethysmography and verified via brachial auscultation. Whole-body heat stress to raise oral temperature 0.8 °C above baseline was induced via water-perused suits. Cutaneous vascular conductance (CVC) was calculated as LDF/mean arterial pressure and normalized to maximal (%CVC max) via infusion of 28 mm nitroprusside and local heating to 43 °C. There was no difference between control (65 ± 5%CVC max) and theophylline (63 ± 5%CVC max) sites. L-NAME (44 ± 4%CVC max) and theophylline + L-NAME (32 ± 3%CVC max) sites were significantly attenuated compared to both control and theophylline only sites (P<0.05), and combined theophylline + L-NAME sites were significantly reduced compared to L-NAME only sites (P<0.05). These data suggest A1/A2 adenosine receptor activation does not directly contribute to cutaneous active vasodilatation; however, a role for A1/A2 adenosine receptor activation is unmasked when NO synthase is inhibited.