Blocking effects of alinidine on negative chronotropic and inotropic responses to vagal stimulation and injected acetylcholine and carbachol in dogs

Abstract

The effects of alinidine on negative chrono- and inotropic responses to cholinergic interventions, i.e., intramural vagal nerve stimulation and an injection of acetylcholine (ACh) or carbachol, were investigated in isolated, blood-perfused canine atrial preparations perfused by arterial blood from donor dogs. Vagal nerve stimulation (5, 10 or 30 Hz) and an injection of ACh (0.17-1.65 nmol) or carbachol (0.05-0.55 nmol) induced frequency-dependent and dose-dependent negative chrono- and inotropic responses, respectively. These responses were reproducible in the same preparation. During the negative chrono- and inotropic responses to alinidine (85-854 nmol), cardiac responses to cholinergic interventions were depressed dose-dependently. The depressive effects of alinidine on the negative chronotropic responses were significantly (P less than .05) greater than those on the negative inotropic ones. However, alinidine did not affect adenosine-induced negative cardiac responses. Atropine (0.43-4.32 nmol) uniformly blocked responses to cholinergic intervention dose-dependently. The potency of the antimuscarinic effect of alinidine was approximately 1/200 to 1/500 of the potency of atropine at the 50% inhibition dose for responses to vagal stimulation, carbachol and ACh. Intravenous administration of alinidine (1 mg/kg) to the donor dog also suppressed cardiac responses to choline esters and vagal stimulation in the isolated atrium perfused by the donor's blood. These results suggest that alinidine has suppressive effects on the negative chrono- and inotropic responses to exogenous choline esters and endogenous ACh from parasympathetic nerve terminals at the post-junctional cholinergic muscarinic receptors in the dog heart.