Adenosine receptor inhibition attenuates the decrease in cutaneous vascular conductance during whole‐body cooling from hyperthermia

Abstract

New Findings r What is the central question of this study?Adenosine has been implicated in mediating both vasoconstriction and vasodilatation in a variety of tissues throughout the body. No study has yet examined its influence in cutaneous vasoconstriction elicited by whole-body cooling from normothermia or from hyperthermia. r What is the main finding and its importance?Through the use of the non-selective adenosine receptor antagonist, theophylline, a role for adenosine in the control of the cutaneous circulation when cooling from a state of hyperthermia is suggested.Adenosine has both vasodilatory and vasoconstrictive properties, yet its influence on cutaneous vascular conductance (CVC) during whole-body cooling remains unknown. The present study evaluated the influence of adenosine on reflex cutaneous vasoconstriction. Four microdialysis probes were inserted into the dorsal forearm skin of eight subjects and infused with the following solutions: (i) lactated Ringer solution (CON); (ii) 4 mm theophylline (Theo), a non-selective adenosine receptor antagonist; (iii) 10 mm l-NAME, an inhibitor of nitric oxide synthase; and (iv) combined 4 mm theophylline and 10 mm l-NAME (Theo + l-NAME). Subjects subsequently donned a water-perfusion garment. Following a thermoneutral baseline period, the suit was perfused with water at 10• C for 20 min (Cooling 1). The suit was then perfused with water at 49• C for 45 min (Heating), followed by a second cooling period of 20 min using 10 • C water (Cooling 2). Cutaneous blood flow (laser-Doppler) was measured over each microdialysis probe and used to calculate CVC as a percentage of the maximum determined by sodium nitroprusside infusion and local heating. Cutaneous vascular conductance was significantly elevated at the Theo site relative to CON following Cooling 1 (18 ± 6 versus 8 ± 2%; P = 0.01) and Cooling 2 (27 ± 11 versus 14 ± 5%; P = 0.022). Likewise, CVC at the Theo + l-NAME site remained greater compared with l-NAME after Cooling 1 (13 ± 4 versus 7 ± 3%; P = 0.030) and Cooling 2 (15 ± 3 versus 9 ± 2%; P = 0.009). The present findings demonstrate that non-selective antagonism of adenosine receptors attenuates the decrease in cutaneous vascular conductance during wholebody cooling from hyperthermia.

Adenosine receptor inhibition attenuates the suppression of postexercise cutaneous blood flow

“…Consistent with these findings (Swift et al . ), our results show that the infusion of THEO attenuated the decrease in cutaneous blood flow during recovery from exercise‐induced hyperthermia when compared to a control site. In fact, our data show that adenosine receptor activation may be a major contributor to the postexercise suppression in cutaneous blood flow (Fig.…”

“…In keeping with animal studies, however, adenosine receptors have also been shown to modulate CVC during whole‐body cooling (Swift et al . ). This was evidenced by an attenuated decrease in CVC when adenosine receptors were inhibited during a bout of whole‐body cooling that was performed immediately following a passive heat stress.…”

“…To this end, a recent study has identified a role for adenosine receptors in mediating the reduction in cutaneous blood flow during whole‐body cooling from hyperthermia (Swift et al . ). Furthermore, Kalsi and Gonzalez‐Alonso () recently reported that plasma concentrations of ATP were strongly associated with muscle temperature during passive heating and exercise.…”

The mechanisms underlying the muscle metaboreflex modulation of sweating and cutaneous blood flow in passively heated humans

“…; Wong ; Swift et al. ). Moreover, we detected a vasoconstrictor effect of adenosine receptors on baseline CVC under low heat stress (Fieger and Wong ; McGinn et al.…”

“…; Swift et al. ). However, it is important to note that the level of influence of NOS, COX, and adenosine receptors to cutaneous blood flow and sweating can vary based on the type and level of heating (Kellogg et al.…”