RESPONSE OF ISOLATED GUINEA-PIG ATRIA TO VARIOUS GANGLION-STIMULATING AGENTS

¹ Department of Pharmacology, College of Medicine, Howard Univercity, Washington, D.C.

Nicotine has long been known as having a biphasic action on the isolated heart. The initial negative response is due to stimulation of parasympathetic ganglia, but the significance of the secondary positive response is the subject of much controversy. In order to gain further information on this point, effects of nicotine on the isolated guinea-pig heart were compared with the effects of other ganglion stimulants, dimethylphenylpiperazinium iodide (DMPP) and 4-(m-chlorophenyl carbamoyloxy)-2-butynyl-trimethylammonium chloride (McN-A-343), in the presence of atropine. All these ganglion stimulants exhibited positive cardiostimulant effects. These responses were prevented by treatment of the animal with reserpine or by addition of dichloroisoproterenol hydrochloride, bretylium or cocaine to the organ bath. The effect of these stimulants was restored by incubation of the reserpine-pretreated atria with norepinephrine. Hexamethonium, chlorisondamine, hemicholinium and 3,6-bis(3-diethylaminopropoxy)pyridazine bis-methiodide, while successfully antagonizing the responses to nicotine, failed to affect the response to DMPP or McN-A-343. The previously reported blockade of the response to McN-A-343 by atropine was not observed. It is concluded that the cardiostimulatory actions of ganglionic stimulants are not dependent on the presence of ganglia and that ganglionic stimulants produce these effects by liberating catecholamines directly from stores in the nerve endings. The antinicotinic activity of hexamethonium and hemicholinium is peripheral. McN-A-343 acts on guinea-pig atria in a different manner.