K-ATP+ channels, nitric oxide, and adenosine are not required for local metabolic coronary vasodilation

The role of ATP-sensitive K+ (K-ATP(+)) channels, nitric oxide, and adenosi ne in coronary exercise hyperemia was investigated. Dogs (n = 10) were chro nically instrumented with catheters in the aorta and coronary sinus and ins trumented with a flow transducer on the circumflex coronary artery. Cardiac interstitial adenosine concentration was estimated from arterial and coron ary venous plasma concentrations using a previously tested mathematical mod el. Experiments were conducted at rest and during graded treadmill exercise with and without combined inhibition of K-ATP(+) channels (glibenclamide, 1 mg/kg iv), nitric oxide synthesis (N-omega-nitro-L-arginine, 35 mg/kg iv) , and adenosine receptors (8-phenyltheophylline, 3 mg/kg iv). During contro l exercise, myocardial oxygen consumption increased similar to2.9-fold, cor onary blood flow increased similar to2.6-fold, and coronary venous oxygen t ension decreased from 19.9 +/- 0.4 to 13.7 +/- 0.6 mmHg. Triple blockade di d not significantly change the myocardial oxygen consumption or coronary bl ood flow response during exercise but lowered the resting coronary venous o xygen tension to 10.0 +/- 0.4 mmHg and during exercise to 6.2 +/- 0.5 mmHg. Cardiac adenosine levels did not increase sufficiently to overcome the ade nosine receptor blockade. These results indicate that combined inhibition o f K-ATP(+) channels, nitric oxide synthesis, and adenosine receptors lowers the balance between total oxygen supply and consumption at rest but that t hese factors are not required for local metabolic coronary vasodilation dur ing exercise.