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 (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 PO(2) versus MVO(2) relationship steepened. These findings indicate that K(ATP) channels contribute to local metabolic coronary vasodilation in alloxan-induced diabetic dogs.
Tune
Johnathan D
JD
Department of Integrative Physiology, University of North Texas Health Science Center, Fort Worth, Texas 76107, USA. jtune@hsc.unt.edu
Yeh
Clement
C
Setty
Srinath
S
Downey
H Fred
HF
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004285:Dogs; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects; D010313:Partial Pressure; D015221:Potassium Channels; D014664:Vasodilation / Q000502:physiology*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D008565:Membrane Proteins; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D010100:Oxygen; D005905:Glyburide