Mechanism of Chronotropic and Inotropic Effects of Phenylephrine

The effects of phenylephrine and mcthoxamine were studied on pacemaker activity in the sinoatrial node and on atrial and ventricular contractility in isolated, blood-perfused atrial and ventricular preparations of dogs. Each drug was administered directly into the cannulated sinus node artery of an isolated atrium or the anterior descending branch of the isolated left ventricle over a period of 4 sec. Two response patterns to phenylephrine were observed in atrial preparations: monophasic positive chronotropic and inotropic effects: double peaked effects, positive effects were temporarily interrupted by negative effects. Phenylephrine induced positive effects were blocked by an adrenergic beta-blocker, alprenolol or carteolol, but not by desipramine or phentolamine. Phenylephrine-induced negative effects were inhibited by atropine, tetrodotoxin or phentolamine. In ventricular preparations, phenylephrine usually induced a monophasic positive inotropic effect which was completely blocked by a beta-blocker but not by phentolamine. On the other hand, mcthoxamine usually induced negative chronotropic and inotropic effects in both preparations, and these negative effects were not blocked by atropine, tetrodotoxin and phentolamine. These results suggest that phenylephrine produces a cholinergic excitation which may occur through an adrenergic alpha-mechanism in parasympathetic nerve terminals, in addition to its adrenergic beta-stimulating effect.