The influence of lactic acid on adenosine release from skeletal muscle in anaesthetized dogs

Abstract

In anaesthetized and artificially ventilated dogs, a gracilis muscle was vascularly isolated and perfused at a constant flow rate of 11.9 ± 2.2 ml min-1 100 g-1 (mean ± S.E.M., n = 16; equivalent to 170.2 ± 21.3% of its resting free flow). Stimulation (3 Hz) of the obturator nerve produced twitch contractions of the gracilis muscle, reduced venous pH from 7.366 ± 0.027 to 7.250 ± 0.031 (n = 5), increased oxygen consumption from 0.62 ± 0.24 to 2.76 ± 0.46 ml min-1 100 g-1 (n = 5) and increased adenosine release from -0.40 ± 0.14 (net uptake) to 1.36 ± 0.50 nmol min-1 100 g-1 (n = 8). Infusion of lactic acid (4.2 mM) into the artery reduced venous pH to 7.281 ± 0.026 (n = 5) and increased adenosine release to 0.96 ± 0.40 nmol min-1 100 g-1 (n = 8), but did not significantly alter oxygen consumption (0.80 ± 0.19 ml min-1 100 g-1; n = 5). Stimulation (3 Hz) in the presence of lactic acid infusion produced no further significant changes in venous pH or adenosine release, but increased oxygen consumption to 2.53 ± 0.37 ml min-1 100 g-1 (n = 5). Infusion of a range of lactic acid concentrations (≥ 1.83 mM) produced dose-dependent increases in adenosine release. The maximum lactic acid concentration tested (5.95 mM) reduced venous pH to 7.249 ± 0.023 (n = 5) and increased adenosine release to 2.64 ± 1.26 nmol min-1 100 g-1 (n = 6). A strong correlation existed between the adenosine release and the venous pH (r = -0.92); points obtained during muscle stimulation and/or lactic acid infusion fell on a single correlation line. The vasoactivity of adenosine administered by close-arterial injection was unaltered by infusion of either lactic acid (7.2 mM) or saline. These results suggest that the release of adenosine from skeletal muscle can be induced by a decrease in pH (probably at an intracellular site), and that this mechanism may contribute to the release of adenosine during muscle contractions.