Autonomic modulation of aminophylline influence on the electrophysiological effects of adenosine and adenosine triphosphate in the canine heart

Summary: The influence of aminophylline, a competitive antagonist of adenosine, on the chronotropic and dromotropic effects of adenosine and adenosine triphosphate was studied in pentobarbital anaesthetised dogs under various modifications of the autonomic nervous tone. Adenosine and adenosine triphosphate (3 μmol·kg^-1 each) were rapidly (≤1 s) injected into the right atrium during both sinus rhythm and right atrial pacing (cycle length 300 ms) before and after infusion of aminophylline (5 mg·kg^-1) (n=21) as well as after increasing doses of aminophylline (n=10). Some dogs underwent either muscarinic blockade with atropine (0.2 mg·kg^-1) (n=10), or beta adrenergic blockade with propranolol (1 mg·kg^-1) (n=10), or complete autonomic blockade with atropine and propranolol (n=10). Aminophylline (5 mg·kg^-1) antagonised the negative chronotropic and dromotropic effects of adenosine triphosphate and adenosine in dogs pretreated with atropine or atropine plus propranolol but did not affect them in autonomically intact dogs. In addition, the electrophysiological effects of adenosine were antagonised by only the highest doses of aminophylline in autonomically intact dogs and by aminophylline (5 mg·kg^-1) in dogs pretreated with propranolol.It was concluded that (a) alteration of the electrophysiological effects of adenosine triphosphate and adenosine by aminophylline is appreciably influenced by the autonomic nervous tone and (b) autonomic blockade is required for the manifestation of the antagonism by aminophylline of the electrophysiological action of adenosine and adenosine triphosphate.