HYDROXYMALONATE INHIBITS LACTATE UPTAKE BY THE RABBIT HINDLIMB

Lactate uptake by skeletal muscle occurs under diverse conditions, inc luding hypoxia and electrical stimulation. A possible metabolic fate o f lactate in resting muscle is its conversion to pyruvate followed by carboxylation to malate in the cytosolic malic reaction. To test this hypothesis, we measured hindlimb lactate uptake in hypoxic mechanicall y ventilated rabbits. Rabbits were given intravenous infusions of hydr oxymalonate, an inhibitor of the malic reaction (200 mM; n = 7), or no rmal saline (n = 7) at 1.1 ml/min. Hindlimb lactate uptake/release was calculated as femoral blood flow times the arteriovenous lactate diff erence. Saline or hydroxymalonate was infused continuously during sequ ential 30-min periods of normoxia (arterial Po-2 approximate to 150 To rr), hypoxemia (arterial Po-2 approximate to 30 Torr), and reoxygenati on (arterial Po-2 approximate to 150 Torr). Hindlimb O-2 transport dec reased with hypoxemia, but O-2 consumption remained unchanged in both groups. During hyperemia there was net uptake of lactate by the hindli mb of the group given normal saline [4.5 +/- 0.9 (SE) mu mol/min]. The hindlimb of the hydroxymalonate group continued to release lactate (- 0.5 +/- 1.0 mu mol/min). The inhibition of lactate uptake by hydroxyma lonate supports the hypothesis that the melic reaction plays a major r ole in the metabolism of lactate by resting rabbit skeletal muscle.