INTRACELLULAR LACTATE CONTROLS ADENOSINE OUTPUT FROM DOG GRACILIS MUSCLE DURING MODERATE SYSTEMIC HYPOXIA

The influence of systemic hypoxia on lactate and adenosine output from isolated constant-flow-perfused gracilis muscle was determined in ane sthetized dogs. The lactate transport inhibitor alpha-cyano-4-hydroxyc innamic acid (CHCA) was employed to distinguish the direct effects of hypoxia on adenosine output from the effects produced indirectly by a change in lactate concentration. Reduction of arterial Po-2 from 135 /- 4 to 39 +/- 2 mmHg raised arterial lactate from 1.26 +/- 0.32 to 2. 22 +/- 0.45 mM but decreased venoarterial lactate difference from 0.53 +/- 0.09 to -0.13 +/- 0.19 mM, indicating that lactate output from th e muscle was abolished. Arterial adenosine did not change, but venoart erial adenosine difference increased from 20.6 +/- 10.1 to 76.5 +/- 14 .4 nM. CHCA infusion during hypoxia abolished adenosine output from gr acilis muscle (venoarterial adenosine difference = -20.5 +/- 40.6 nM). In isolated rat soleus muscle fibers, intracellular pH increased from 6.96 +/- 0.04 to 7.71 +/- 0.14 in response to a reduction of Po-2 fro m 459 +/- 28 to 53 +/- 3 mmHg. Correspondingly, adenosine output decre ased from 3.71 +/- 0.15 to 3.04 +/- 0.27 nM. These data suggest that h ypoxia did not directly stimulate adenosine output from red oxidative skeletal muscle, but rather systemic hypoxia increased lactate deliver y and the resulting increase in intracellular lactate decreased intrac ellular pH, which stimulated adenosine output.