Effects of phentolamine on the SA node of the dog heart in situ.

Direct perfusion of the sinus node artery at constant pressure of 100 mmHg was arranged in 6 canine hearts in situ. The injection of phentolamine into the sinus node artery usually induced dose-dependent positive chronotropic effect. However, at a larger dose of 300 mug, phentolamine frequently induced a biphasic chronotropic response, i.e., sinus deceleration followed by sinus acceleration. Phentolamine at a large dose of 1 mg usually induced a negative chronotropic effect. The threshold dose for inducing sinus acceleration was about 1 to 10 mug. The positive chronotropic response to phentolamine was blocked either by propranolol or by tetrodoxin. That to norepinephrine was blocked by propranolol but not suppressed by tetrodotoxin. These results suggest that the phentolamine-induced sinus acceleration is due to catecholamine which is released by excitation of local adrenergic fibers. The sinus deceleration to higher doses of phentolamine was not blocked either by atropine or by tetrodotoxin. It suggests that phentolamine has a direct depressive effect on the SA node at extremely high dose levels.