Further Evidence Against Adenosine-Catecholamine Antagonism In Vivo: Investigations with Treadmill Exercise in Dogs

Summary

The coronary dilatory action of adenosine has been known for a long time. This, together with the knowledge of the formation of adenosine in the heart during anoxia, hypoxia, exercise, and stress led to the adenosine hypothesis of coronary blood flow regulation. Since adenosine was shown to abolish or at least to partially reduce the cardiostimulatory effects of isoproterenol in the isolated perfused guinea pig heart, adenosine-catecholamine antagonism was suggested. This antagonism should come into play during sympathetic stimulation and protect the heart from excessive activation. In anesthetized dogs, however, no antagonism between adenosine and isoproterenol was found. To further investigate this proposed antagonism, conscious, chronically instrumented dogs were exercised on a treadmill. Treadmill exercise leads to an increase in heart rate, left ventricular dp/dt, and subendocardial function. Since exercise evokes both sympathetic activation and adenosine formation, cardiac stimulation during exercise should be influenced by drugs which interfere with the action of adenosine if the adenosinecatecholamine antagonistic theory applies. But neither 8-phenyltheophylline, an adenosine receptor antagonist, nor L-homocysteine, which binds adenosine intracellularly, nor hexoben-dine, which enhances the effects of adenosine, had any influence on the exercise-induced increase in heart rate, left ventricular dp/dt or regional subendocardial function. These results confirm data previously obtained in anesthetized dogs and suggest that adenosine-catecholamine antagonism is of no physiological importance in conscious dogs, even during exercise.