Inhibition of glycolysis potentiates hypoxic vasoconstriction in rat lungs

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Abstract
Whether inhibition of glycolysis would potentiate hypoxic vasconstriction in isolated rat lungs, and, if so, whether potentiation was due to decreased aerobic production of the mitochondrial substrate, pyruvate or to inhibition of anaerobic synthesis of ATP was evaluated. 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. Evidently, 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 O2-sensing cell or to a decreased level of some intracellular or intercellular modulating peptide, fatty acid or lipid.

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