Effects of flow and contraction on lactate transport in the perfused rat hindlimb

Abstract

A perfused rat hindlimb preparation was used to assess the effects of perfusate flow and electrical stimulation to mimic exercise on the rates of lactate influx (measured by a dual tracer technique with [3H]mannitol as the extracellular marker) and net lactate production. The same perfused muscle system was also used for assessing the effects of alpha-cyano-4-hydroxycinnamate (CIN, 15 mM), phloretin (0.6 mM), and pyruvate on tracer lactate influx. Unidirectional lactate influx, oxygen uptake (VO2), and net lactate flux were all significantly dependent on perfusate flow rate (all P < 0.05). The hindlimb was in net lactate production at all flow rates studied. Electrical stimulation (60 Hz, 100 ms, 20 V trains at 0.6 min-1) at perfusate lactate concentration of 1 mM significantly increased the hindlimb VO2 from 8.0 +/- 1.1 to 16.0 +/- 2.2 ml.kg-1.min-1 and production of lactate from -69 +/- 31 to -823 +/- 77 nmol.min-1.g-1 (both P < 0.001) but did not affect tracer-measured unidirectional lactate influx (nonstimulated: 235.4 +/- 78.1; stimulated: 235.0 +/- 31.0 nmol.min-1.g-1). At a perfusate flow of 0.55 ml.g-1.min-1 the unidirectional influx of 1 mM lactate was markedly inhibited (90 +/- 5%) by 15 mM CIN. CIN also significantly reduced VO2 from 6.2 +/- 0.16 to 4.45 +/- 0.57 ml.kg-1.min-1 (P < 0.05, n = 5). Phloretin (0.6 mM, n = 3) had no significant effect on lactate influx.(ABSTRACT TRUNCATED AT 250 WORDS)