Role of K-ATP(+) channels and adenosine in regulation of coronary blood flow in the hypertrophied left ventricle

In the hypertrophied heart, increased extravascular forces acting to compre ss the intramural coronary vessels might require augmentation of metabolic vasoldilator mechanisms to maintain adequate coronary blood flow. Vascular smooth muscle ATP-sensitive potassium (K-ATP(+)) channel activity is import ant in metabolic coronary vasodilation, and adenosine contributes to resist ance vessel dilation in the hypoperfused heart. Consequently, this study wa s performed to determine whether K-ATP(+) channels and adenosine have incre ased importance in exercise-induced coronary vasodilation in the hypertroph ied left ventricle. Studies were performed in dogs in which banding of the ascending aorta had resulted in a 66% increase in left ventricular mass in comparison with historic normal animals. Treadmill exercise resulted in inc reases of coronary blood flow that were linearly related to the increase of heart rate or rate-pressure product. During resting conditions, K-ATP(+) c hannel blockade with glibenclamide caused a 17 +/- 5% decrease in coronary blood flow similar to that previously observed in normal hearts. Unlike nor mal hearts, however, glibenclamide blunted the increase in coronary flow th at occurred during exercise, causing a significant decrease in the slope of the relationship between coronary flow and the rate-pressure product. Aden osine receptor blockade with 8-phenyltheophylline did not alter coronary bl ood flow at rest or during exercise. Furthermore, even after K-ATP(+) chann el blockade with glibenclamide, the addition of 8-phenyltheophylline had no effect on coronary blood flow. This finding was different from normal hear ts, in which the addition of adenosine receptor blockade after glibenclamid e impaired exercise-induced coronary vasodilation. The data suggest that, i n comparison with normal hearts, hypertrophied hearts have increased relian ce on opening of K-ATP(+), channels to augment coronary flow during exercis e. Contrary to the initial hypothesis, however, adenosine was not mandatory for exercise-induced coronary vasodilation in the hypertrophied hearts eit her during control conditions or when K-ATP(+) channel activity was blocked with glibenclamide.