EFFECTS OF INSULIN, GLUCOSE ANALOGS, AND PYRUVATE ON VASCULAR-RESPONSES TO ANOXIA IN ISOLATED FERRET LUNGS

In isolated ferret lungs, the vasopressor response to anoxia is charac terized by an intense initial vasoconstriction, followed by marked vas odilation. This hypoxic pulmonary vasodilation (HPVD) is inhibited by perfusate glucose concentration greater-than-or-equal-to 15 mM. To det ermine whether this inhibition of HPVD was mediated by an effect of gl ucose transport or a product of glucose metabolism beyond pyruvate, we studied the effects of 5 mM glucose + insulin, transportable but nonm etabolizable analogues of glucose, and pyruvate on the pulmonary vascu lar response to anoxia. Isolated ferret lungs were ventilated with 28% O2 at constant flow. Perfusate glucose concentration was allowed to f all spontaneously. Thirty-minute anoxic exposures were performed at 60 , 120, and 180 min of perfusion. Before the third anoxic exposure 15 m M glucose, 15 mM sucrose, 5 mM glucose (with 10 mM sucrose) + 10 mU/ml insulin, 15 mM 3-O-methylglucose (3-O-MG), or 15 mM alpha-methylgluco se (alpha-MG) was added to the perfusate and vasomotor responses recor ded. In another series of experiments, 15 mM pyruvate was added to the preparation at the beginning of perfusion. Peak vasoconstrictor respo nses were not different among groups. HPVD was greater in sucrose, ins ulin, 3-O-MG, alpha-MG, and pyruvate lungs than in high glucose lungs. These results suggest that glucose transport or a product of glucose metabolism beyond pyruvate was not responsible for inhibiting HPVD. We speculate that hyperglycemia inhibits HPVD by increasing production o f ATP from the glycolytic pathway and that this ATP inhibits ATP-depen dent K+ channels.