Effects of insulin, glucose analogues, and pyruvate on vascular responses to anoxia in isolated ferret lungs.
In isolated ferret lungs, the vasopressor response to anoxia is characterized by an intense initial vasoconstriction, followed by marked vasodilation. This hypoxic pulmonary vasodilation (HPVD) is inhibited by perfusate glucose concentration > or = 15 mM. To determine whether this inhibition of HPVD was mediated by an effect of glucose transport or a product of glucose metabolism beyond pyruvate, we studied the effects of 5 mM glucose + insulin, transportable but nonmetabolizable analogues of glucose, and pyruvate on the pulmonary vascular response to anoxia. Isolated ferret lungs were ventilated with 28% O2 at constant flow. Perfusate glucose concentration was allowed to fall spontaneously. Thirty-minute anoxic exposures were performed at 60, 120, and 180 min of perfusion. Before the third anoxic exposure 15 mM 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-methylglucose (alpha-MG) was added to the perfusate and vasomotor responses recorded. In another series of experiments, 15 mM pyruvate was added to the preparation at the beginning of perfusion. Peak vasoconstrictor responses were not different among groups. HPVD was greater in sucrose, insulin, 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 of ATP from the glycolytic pathway and that this ATP inhibits ATP-dependent K+ channels.
Wiener
C M
CM
Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland 21205.
Sylvester
J T
JT
D000818:Animals; D005289:Ferrets; D005947:Glucose / Q000031:analogs & derivatives / Q000494:pharmacology*; D006019:Glycolysis / Q000187:drug effects / Q000502:physiology; D006943:Hyperglycemia / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011652:Pulmonary Circulation / Q000187:drug effects*; D011773:Pyruvates / Q000494:pharmacology*; D019289:Pyruvic Acid; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects
D007328:Insulin; D015221:Potassium Channels; D011773:Pyruvates; D019289:Pyruvic Acid; D005947:Glucose