Role of adenosine in the sympathetic activation produced by isometric exercise in humans.

Abstract

Isometric exercise increases sympathetic nerve activity and blood pressure. This exercise pressor reflex is partly mediated by metabolic products activating muscle afferents (metabore- ceptors). Whereas adenosine is a known inhibitory neuromodu- lator, there is increasing evidence that it activates afferent nerves. We, therefore, examined the hypothesis that adenosine stimulates muscle afferents and participates in the exercise pressor reflex in healthy volunteers. Intraarterial administra- tion of adenosine into the forearm, during venous occlusion to prevent systemic effects, mimicked the response to exercise, increasing muscle sympathetic nerve activity (MSNA, lower limb microneurography) and mean arterial blood pressure (MABP) at all doses studied (2, 3, and 4 mg). Heart rate in- creased only with the highest dose. Intrabrachial adenosine (4 mg) increased MSNA by 9625% (n = 6, P < 0.01) and MABP by 123 mmHg (P < 0.01). Adenosine produced forearm dis- comfort, but equivalent painful stimuli (forearm ischemia and cold exposure) increased MSNA significantly less than adeno- sine. Furthermore, adenosine receptor antagonism with intra- brachial theophylline (1 ytg/ml forearm per min) blocked the increase in MSNA (9215% vs. 286%, n = 7, P < 0.01) and MABP (386 vs. 274 mmHg, P = 0.01) produced by isomet- ric handgrip (30% of maximal voluntary contraction) in the in- fused arm, but not the contralateral arm. Theophylline did not prevent the increase in heart rate produced by handgrip, a response mediated more by central command than muscle af- ferent activation. We propose that endogenous adenosine contributes to the activation of muscle afferents involved in the exercise pressor reflex in humans. (J. Clin. Invest.