Effect of metabolic inhibitors on Na+ transport in isolated perfused rat lungs

Alveolar fluid absorption is a process driven by transepithelial alveolar Na+ transport. Since lungs produce significant amounts of lactate under anaerobic but also under aerobic conditions, glycolysis may conceivably contribute to producing the energy needed for transepithelial Na+ transport and fluid absorption. The effects of inhibition of oxidative phosphorylation or glycolysis on alveolar Na+ transport, fluid absorption, and preservation of alveolar epithelial barrier properties were examined using isolated, fluid-filled rat lungs. Basal lung lactate production was 65 +/- 1.0 mumol/h/g dry wt in the presence of 10 mmol/liter glucose. When oxidative phosphorylation was inhibited with rotenone, cyanide, or the uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP), lung lactate production increased 5- to 7-fold within 30 min (P < 0.001). No significant decrease in alveolar Na+ transport was observed over 1 h, whereas a 3-fold increase in passive epithelial permeability was observed. With rotenone and CCCP, but not cyanide, fluid absorption from airspaces was decreased but never abolished. Inhibition of aerobic glycolysis with iodoacetate did not significantly affect alveolar Na+ transport or fluid absorption. In the presence of isoproterenol or dibutyryl cyclic adenosine monophosphate (cAMP) + isobutylmethylxanthine, which have previously been shown to stimulate alveolar Na+ transport, lung lactate production increased 2-fold (P < 0.001). Inhibition of glycolysis depressed stimulated alveolar Na+ and fluid transports (P < 0.001). Inhibition of ion transport by ouabain or amiloride decreased lung lactate production (P < 0.001) under stimulated but not under unstimulated conditions. These observations suggest that glycolysis does not significantly contribute to energy provision for alveolar epithelial Na+ transport in lungs under basal, aerobic conditions.(ABSTRACT TRUNCATED AT 250 WORDS)