Adenosine, a metabolic trigger of the exercise pressor reflex in humans

There is substantial evidence that adenosine activates muscle afferent nerv e fibers leading to sympathetic stimulation, but the issue remains controve rsial. To further test this hypothesis, we used local injections of adenosi ne into the brachial artery while monitoring systemic muscle sympathetic ne rve activity (MSNA) with peroneal microneurography. The increase in MSNA in duced by 3 mg intrabrachial adenosine (106+/-32%) was abolished if forearm afferent traffic was interrupted by axillary ganglionic blockade (21+/-19%, n=5, P<0.05). Furthermore, the increase in MSNA induced by intravenous ade nosine was 3.7-fold lower and later (onset latency 20.9+/-4.8 seconds versu s 8.5+/-1 seconds) than intrabrachial adenosine. Finally, we used forearm e xercise (dynamic handgrip at 50% and 15% maximal voluntary contraction, MVC ), with or without superimposed ischemia, to modulate interstitial levels o f adenosine (estimated with microdialysis) while monitoring MSNA. Fifteen m inutes of intense (50% MVC) and moderate (15% MVC) exercise increased adeno sine dialysate concentrations from 0.31+/-0.1 to 1.24+/-0.4 <mu>mol/L (528/-292%) and from 0.1+/-0.02 to 0.419+/-0.16 mu mol/L (303+/-99%), respectiv ely (n=7, P<0.01). MSNA increased 88+/-25% and 38+/-28%, respectively. Five minutes of moderate exercise increased adenosine from 0.095+/-0.02 to 0.25 +/-0.12 <mu>mol/L, and from 0.095+/-0.02 to 0.48+/-0.19 mu mol/L when ische mia was superimposed on exercise (n=7, P=0.01). The percent increase in MSN A induced by the various interventions correlated with the percent increase in dialysate adenosine levels (r=0.96). We conclude that adenosine activat es muscle afferent nerves, triggering reflex sympathetic activation.