ADENOSINE CONCENTRATIONS IN THE INTERSTITIUM OF RESTING AND CONTRACTING HUMAN SKELETAL-MUSCLE

Background-Adenosine has been proposed to be a locally produced regula tor of blood flow in skeletal muscle. However, the fundamental questio ns of to what extent adenosine is formed in skeletal muscle tissue of humans, whether it is present in the interstitium, and where it exerts its vasodilatory effect remain unanswered. Methods and Results -The i nterstitial adenosine concentration was determined in the vastus later alis muscle of healthy humans via dialysis probes inserted in the musc le. The probes were perfused with buffer, and the dialysate samples we re collected at rest and during graded knee extensor exercise. At rest , the interstitial concentration of adenosine was 220+/-100 nmol/L and femoral arterial blood flow (FaBF) was 0.1+/-0.02 L/min. When the sub jects exercised lightly, at a work rate of 10 W, there was a markedly higher (1140+/-540 nmol/L; P<0.05) interstitial adenosine concentratio n and a higher FaBF (2.22+/-0.18 L/min; P<0.05) compared with at rest. When exercise was performed at 20, 30, 40, or 50 W, the concentration of adenosine was moderately greater for each increment, as was the le vel of leg blood flow. The interstitial concentrations of ATP, ADP, an d AMP increased from rest (0.13+/-0.03, 0.07+/-0.03, and 0.07+/-0.02 m u mol/L, respectively) to exercise (10 W; 2.00+/-1.32, 2.08+/-1.23, an d 1.65+/-0.50 mu mol/L, respectively; P<0.05). Conclusions-The present study provides, for the first time, interstitial adenosine concentrat ions in human skeletal muscle and demonstrates that adenosine and its precursors increase in the exercising muscle interstitium, at a rate a ssociated with intensity of muscle contraction and the magnitude of mu scle blood flow.