Inhibition of glycolysis potentiates hypoxic vasoconstriction in rat lungs.

The purpose of this study was to test whether inhibition of glycolysis would potentiate hypoxic vasoconstriction in isolated rat lungs, and, if so, to evaluate whether potentiation was due to decreased aerobic production of the mitochondrial substrate, pyruvate, or to inhibition of anaerobic synthesis of ATP. In blood-perfused lungs, both iodoacetate and 2-deoxyglucose inhibited lactate production and increased pressor responses to ventilation with gases containing from 15 to 3% O2. In lungs perfused with physiological salt solution, both 2-deoxyglucose and glucose-free perfusion inhibited lactate and pyruvate production and potentiated the dose-response curve to hypoxia. Dose responses to angiotensin II and KCl were not increased by glucose-free perfusion. Lungs perfused with glucose-free salt solution containing increased levels of lactate and pyruvate did not show an increased dose response to hypoxia. In contrast, lungs perfused with the inhibitor of citric acid cycle, malonate, in addition to the increased lactate and pyruvate, did show an increased dose response to hypoxia. These results indicate that potentiation of hypoxic vasoconstriction by inhibition of glucose metabolism is due to decreased production of pyruvate, rather than to decreased glycolytic generation of ATP. The potentiation might be directly related to either limitation of mitochondrial oxidative phosphorylation in an oxygen-sensing cell or to a decreased level of some intra- or intercellular modulating peptide, fatty acid, or lipid.