ENDOGENOUS ADENOSINE MEDIATES CORONARY VASODILATION DURING EXERCISE AFTER K-ATP(+) CHANNEL BLOCKADE

The mechanism of coronary vasodilation produced by exercise is not und erstood completely. Recently, we reported that blockade of vascular sm ooth muscle K-ATP(+) channels decreased coronary blood flow at rest, b ut did not attenuate the increments in coronary flow produced by exerc ise. Adenosine is not mandatory for maintaining basal coronary flow, o r the increase in how produced by exercise during normal arterial infl ow, but does contribute to coronary vasodilation in hypoperfused myoca rdium. Therefore, we investigated whether adenosine opposed the hypope rfusion produced by K-ATP(+) channel blockade, thereby contributing to coronary vasodilation during exercise. 11 dogs were studied at rest a nd during exercise under control conditions, during intracoronary infu sion of the K-ATP(+) channel blocker glibenclamide (50 mu g/kg per min ), and during intracoronary glibenclamide in the presence of adenosine receptor blockade. Glibenclamide decreased resting coronary blood flo w from 45+/-5 to 35+/-4 ml/min (P < 0.05), but did not prevent exercis e-induced increases of coronary flow. Glibenclamide caused an increase in myocardial oxygen extraction at the highest level of exercise with a decrease in coronary venous oxygen tension from 15.5+/-0.7 to 13.6/-0.8 mmHg (P < 0.05). The addition of the adenosine receptor antagoni st 8-phenyltheophylline (5 mg/kg intravenous) to K-ATP(+) channel bloc kade did not further decrease resting coronary blood flow but did atte nuate the increase in coronary flow produced by exercise. This was acc ompanied by a further decrease of coronary venous oxygen tension to 10 .1+/-0.7 mmHg (P < 0.05), indicating aggravation of the mismatch betwe en oxygen demand and supply. These findings are compatible with the hy pothesis that K-ATP(+) channels modulate coronary vasomotor tone both under resting conditions and during exercise. However, when K-ATP(+) c hannels are blocked, adenosine released from the hypoperfused myocardi um provides an alternate mechanism to mediate coronary vasodilation in response to increases in oxygen demand produced by exercise.