ATP-dependent K(+) channels contribute to local metabolic coronary vasodilation in experimental diabetes

Diabetes
Johnathan D TuneH Fred Downey

Abstract

This study tested whether ATP-dependent K(+) channels (K(ATP) channels) are an important mechanism of functional coronary hyperemia in conscious, instrument-implanted diabetic dogs. Data were collected at rest and during exercise before and after induction of diabetes with alloxan monohydrate (40-60 mg/kg intravenously). K(ATP) channels were inhibited with glibenclamide (1 mg/kg intravenously). In nondiabetic dogs, arterial plasma glucose concentration increased from 4.8 +/- 0.3 to 21.5 +/- 2.2 mmol/l 1 week after alloxan injection. In nondiabetic dogs, exercise increased myocardial oxygen consumption (MVO(2)) 3.4-fold, myocardial O(2) delivery 3.0-fold, and heart rate 2.4-fold. Coronary venous PO(2) decreased from 19.9 +/- 0.8 mmHg at rest to 14.8 +/- 0.8 mmHg during exercise. Diabetes significantly reduced myocardial O(2) delivery and lowered coronary venous PO(2) from 16.3 +/- 0.6 mmHg at rest to 13.1 +/- 0.9 mmHg during exercise. Glibenclamide did not alter the slope of the coronary venous PO(2) versus MVO(2) relationship in nondiabetic dogs. In diabetic dogs, however, glibenclamide further reduced myocardial O(2) delivery; coronary venous PO(2) fell to 9.0 +/- 1.0 mmHg during exercise, and the slope of the coronary venous ...Continue Reading

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Citations

Aug 2, 2011·Cardiovascular Research·Tineke van de WeijerPatrick Schrauwen
Jan 2, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Léna BorbouseJohnathan D Tune
Mar 25, 2009·Experimental Biology and Medicine·Shawn B BenderM Harold Laughlin
Jul 20, 2011·Journal of Molecular and Cellular Cardiology·Zachary C BerwickJohnathan D Tune
Aug 10, 2006·American Journal of Physiology. Renal Physiology·Giovanna GiannicoJerry Yee
Jan 12, 2020·Cardiovascular Research·Oana SoropDirk J Duncker
Mar 27, 2004·Experimental Biology and Medicine·Pu ZongH Fred Downey

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