Venous adenosine content and vascular responses in dog hind-limb skeletal muscles during twitch contraction.

In dogs anaesthetized with pentobarbitone sodium and chloralose and artificially ventilated, the skeletal muscles of a hind limb were vascularly and neurally isolated and perfused at a constant flow of 150% of the resting blood flow (5.8 +/- 0.3 ml.min-1.100g-1 muscle tissue, mean +/- S.E.M., n = 6) obtained after denervation of the limb. Electrical stimulation of the cut peripheral ends of the femoral and sciatic nerves for 20 min resulted in muscle contraction and a decrease in arterial perfusion pressure to a new steady level (59.7 +/- 8.6% decrease in vascular resistance) within 2 min; the pressure remained constant throughout the remaining 20 min. Similarly venous oxygen tension decreased from 38.2 +/- 1.3 (control) to 16.4 +/- 1.7 mmHg (n = 5) during contractions. The concentration of adenosine in arterial plasma did not change significantly during muscle contraction (122.5 +/- 28 nM, n = 8). However, the adenosine concentrations in venous plasma increased significantly (P less than 0.05) from a control value of 94.8 +/- 33 nM (n = 8) to 256 +/- 82 nM (n = 8) after 10 min and 235 +/- 31 nM (n = 8) after 20 min of muscle contraction. During infusion of adenosine into the femoral artery to give a range of arterial plasma concentrations between 0.17 and 90 microM, 89.2 +/- 2.8% (n = 20) of the infused adenosine was removed (taken up by tissues) from the blood before it reached the vein. Infusion of adenosine caused dose-dependent decreases in vascular resistance ranging between 7 and 79%; 5.58 +/- 1.50 microM adenosine caused a decrease in resistance of 36.1 +/- 7.1% (n = 10) and 51.7 +/- 7.4 microM adenosine caused a decrease of 51.2 +/- 4.1% (n = 9). Comparison of venous plasma adenosine concentrations during adenosine infusions with those seen during contractions suggests that the released adenosine can contribute about 60% of the total vasodilatation seen during contractions of the muscle. These results show that adenosine appears in the venous blood during muscle contraction and is likely to contribute to exercise hyperaemia.