HIGHLIGHTED TOPIC Skeletal and Cardiac Muscle Blood Flow -Adrenoceptor-mediated coronary vasoconstriction is augmented during exercise in experimental diabetes mellitus

Setty, Srinath, Wei Sun, Rodolfo Martinez, H. Fred Downey, and Johnathan D. Tune. -Adrenoceptor-mediated coronary vasoconstriction is augmented during exercise in experimental diabetes mellitus. J Appl Physiol 97: 431–438, 2004. First published February 20, 2004; 10.1152/japplphysiol.01122.2003.—This study tested whether -adrenoceptor-mediated coronary vasoconstriction is augmented during exercise in diabetes mellitus. Experiments were conducted in dogs instrumented with catheters in the aorta and coronary sinus and with a flow transducer around the circumflex coronary artery. Diabetes was induced with alloxan monohydrate (n 8, 40 mg/kg iv). Arterial plasma glucose concentration increased from 4.7 0.2 mM in nondiabetic, control dogs (n 8) to 21.4 1.9 mM 1 wk after alloxan injection. Coronary blood flow, myocardial oxygen consumption (MV̇O2), aortic pressure, and heart rate were measured at rest and during graded treadmill exercise before and after infusion of the -adrenoceptor antagonist phentolamine (1 mg/kg iv). In untreated diabetic dogs, exercise increased MV̇O2 2.7-fold, coronary blood flow 2.2-fold, and heart rate 2.3-fold. Coronary venous PO2 fell as MV̇O2 increased during exercise. After -adrenoceptor blockade, exercise increased MV̇O2 3.1-fold, coronary blood flow 2.7-fold, and heart rate 2.1-fold. Relative to untreated diabetic dogs, -adrenoceptor blockade significantly decreased the slope of the relationship between coronary venous PO2 and MV̇O2. The difference between the untreated and phentolamine-treated slopes was greater in the diabetic dogs than in the nondiabetic dogs. In addition, the decrease in coronary blood flow to intracoronary norepinephrine infusion was significantly augmented in anesthetized, open-chest, -adrenoceptor-blocked diabetic dogs compared with the nondiabetic dogs. These findings demonstrate that -adrenoceptor-mediated coronary vasoconstriction is augmented in alloxan-induced diabetic dogs during physiological increases in MV̇O2.