title: Insulin increases glycolysis without further vasodilation in porcine coronary arteries exposed to hypoxia.
abstract: In acute ischaemia, glucose-insulin-potassium administration reduces mortality and beta-adrenoceptor antagonists have favourable effects on the outcome of ischaemic heart disease. The present study was designed to investigate whether insulin (1.4x10(-7) M) and the beta-adrenoceptor antagonist, propranolol (10(-5) M), increase hypoxic vasodilation in correspondence with changes in glycolysis. Porcine coronary arteries, precontracted with 10(-5) M prostaglandin F(2alpha), were mounted in a pressure myograph and a microdialysis catheter was inserted in the tunica media. Hypoxic vasodilation, interstitial lactate/pyruvate ratio and interstitial glucose were measured at low (2 mM) and high (20 mM) glucose concentrations. Hypoxia (60 min) caused vasodilation and doubled the lactate/pyruvate ratio. Treatment with insulin quadrupled the lactate/pyruvate ratio during hypoxia, but did not change hypoxic vasodilation. Propranolol blocked isoprenaline-evoked vasodilation, but hypoxic increases in lactate/pyruvate ratio and vasodilation did not change. The combination of insulin and propranolol did not cause further changes compared with each drug added alone, although the combination increased vasoconstriction during reoxygenation. Interstitial glucose fell during hypoxia at an organ bath glucose concentration of 2 mM, and rose at a glucose concentration of 20 mM. Addition of insulin and propranolol alone or in combination had no effect on interstitial glucose concentration. Accordingly, arteries were found to contain only minute amounts of the glucose transporter isoform GLUT4. Our findings suggest that insulin increases arterial glycolysis, but treatment with insulin, propranolol, or both, is not associated with enhanced coronary vasodilation during hypoxia.
authors.affiliation: Department of Cardiology S, Aalborg University Hospital, DK-900 Aalborg, Denmark. frobert@dadlnet.dk
authors.forename: Ole
authors.initials: O
authors.lastname: Frøbert
authors.forename: Jens P
authors.initials: JP
authors.lastname: Bagger
authors.forename: Ulf
authors.initials: U
authors.lastname: Simonsen
authors.forename: Sten
authors.initials: S
authors.lastname: Lund
authors.forename: Claus H
authors.initials: CH
authors.lastname: Gravholt
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005947:Glucose / Q000032:analysis; D051275:Glucose Transporter Type 4; D006019:Glycolysis / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D007328:Insulin / Q000494:pharmacology*; D007773:Lactates / Q000032:analysis; D017551:Microdialysis / Q000379:methods; D009004:Monosaccharide Transport Proteins / Q000032:analysis; D009124:Muscle Proteins; D011433:Propranolol / Q000494:pharmacology; D011773:Pyruvates / Q000032:analysis; D013552:Swine; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D007773:Lactates; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D011773:Pyruvates; D014665:Vasodilator Agents; D011433:Propranolol; D005947:Glucose