Role of adenosine in norepinephrine-induced coronary vasodilation

Adenosine has been postulated to be the physiological transmitter coupling increases in coronary blood flow to increases in myocardial metabolism. The purpose of this experiment was to evaluate the role of adenosine in the coronary hyperemia due to norepinephrine. In 11 anesthetized, closed-chest canine preparations, the left main coronary artery was cannulated and perfused with blood at 100 mmHg. Coronary blood flow and myocardial oxygen consumption were measured, and interstitial adenosine concentration was estimated from arterial and coronary venous measurements using a distributed model. Adenosine receptor blockade with 8-phenyltheophylline (8-PT) was used to shift the adenosine dose-response curve 12-fold. During intracoronary norepinephrine infusion, coronary blood flow and myocardial oxygen consumption increased similarly before and after 8-PT, demonstrating a lack of an effect from the adenosine receptor blockade. Before 8-PT, estimated interstitial adenosine increased to a vasoactive concentration (220 nM); however, the temporal correlation with coronary blood flow was poor. After 8-PT, a similar increase in estimated interstitial adenosine was found, demonstrating that there was no augmentation in adenosine concentration to overcome the adenosine receptor blockade. Thus adenosine could not be responsible for the increase in coronary blood flow after adenosine receptor blockade and therefore is not required for norepinephrine-induced hyperemia.