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

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 (MVo₂) 3.4-fold, myocardial O₂ delivery 3.0-fold, and heart rate 2.4-fold. Coronary venous Po₂ decreased from 19.9 ± 0.8 mmHg at rest to 14.8 ± 0.8 mmHg during exercise. Diabetes significantly reduced myocardial 02 delivery and lowered coronary venous Po₂ 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 PO₂ versus MVo₂ relationship in nondiabetic dogs. In diabetic dogs, however, glibenclamide further reduced myocardial O₂ delivery; coronary venous Po₂ fell to 9.0 ± 1.0 mmHg during exercise, and the slope of the coronary venous PO₂ versus MVo₂ relationship steepened. These findings indicate that KATP channels contribute to local metabolic coronary vasodilation in alloxan-induced diabetic dogs.