In acute ischaemia, glucose–insulin–potassium administration reduces mortality and β-adrenoceptor antagonists have favourable effects on the outcome of ischaemic heart disease. The present study was designed to investigate whether insulin (1.4×10−7 M) and the β-adrenoceptor antagonist, propranolol (10−5 M), increase hypoxic vasodilation in correspondence with changes in glycolysis. Porcine coronary arteries, precontracted with 10−5 M prostaglandin F2α, 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.
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August 2004
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Research Article|
July 27 2004
Insulin increases glycolysis without further vasodilation in porcine coronary arteries exposed to hypoxia
Ole FRØBERT;
*Department of Cardiology S, Aalborg University Hospital, DK-900 Aalborg, Denmark
†Department of Pharmacology, University of Aarhus, DK-8000 Aarhus C, Denmark
Correspondence: Dr Ole Frøbert (email [email protected]).
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Jens P. BAGGER;
Jens P. BAGGER
‡Imperial College School of Medicine, Department of Cardiology, Hammersmith Hospital, London W12 0HS, U.K.
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Ulf SIMONSEN;
Ulf SIMONSEN
†Department of Pharmacology, University of Aarhus, DK-8000 Aarhus C, Denmark
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Sten LUND;
Sten LUND
§Department of Endocrinology M, University Hospital Aarhus, DK-8000 Aarhus C, Denmark
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Claus H. GRAVHOLT
Claus H. GRAVHOLT
§Department of Endocrinology M, University Hospital Aarhus, DK-8000 Aarhus C, Denmark
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Publisher: Portland Press Ltd
Received:
January 08 2004
Revision Received:
March 10 2004
Accepted:
April 07 2004
Accepted Manuscript online:
April 07 2004
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society
2004
Clin Sci (Lond) (2004) 107 (2): 213–220.
Article history
Received:
January 08 2004
Revision Received:
March 10 2004
Accepted:
April 07 2004
Accepted Manuscript online:
April 07 2004
Citation
Ole FRØBERT, Jens P. BAGGER, Ulf SIMONSEN, Sten LUND, Claus H. GRAVHOLT; Insulin increases glycolysis without further vasodilation in porcine coronary arteries exposed to hypoxia. Clin Sci (Lond) 1 August 2004; 107 (2): 213–220. doi: https://doi.org/10.1042/CS20040006
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