Neurotransmitter Control of Sinoatrial Pacemaker Frequency in Isolated Rat Atria and in Intact Rabbits

The sinoatrial node is under the control of both parasympathetic and sympathetic influences. To study the interaction between these opposing influences, the response of the frequency of contraction of a spontaneously contracting rat right atrium to combinations of the neurotransmitters, norepinephrine and acetylcholine was observed. Norepinephrine in concentrations of 1 × 10-7M, 1 × 10-6M, and 1 × 10-5M, which by themselves increased atrial frequency by averages of 30%, 51% and 82%, respectively, and acetylcholine in concentrations of 1 × 10-5M, 1 × l0-4M, and 1 × 10-3M, which by themselves decreased atrial frequency by averages of 17%, 52%, and 97%, respectively, were added in all combinations to the atrial preparations. The response was not an algebraic sum of the effects of each of the agents; rather, the bradycrotic influence of acetylcholine predominated in all cases. This action of acetylcholine was blocked by atropine. To evaluate this interaction under more physiologic circumstances, the response of heart rate of anesthetized rabbits to isoproterenol, a potent beta-receptor stimulant, and to asphyxia, a stimulus which produces a marked parasympathetic discharge, was studied. Asphyxia alone induced a marked bradycardia that could be abolished by vagotomy. However, this bradycardia was not prevented by isoproterenol. It is concluded that the predominance of the parasympathetic nervous system on the sinoatrial frequency is a result of the interaction of the neurotransmitters, norepinephrine and acetylcholine on the sinoatrial node. In this interaction the presence of acetylcholine appears to prevent the action of norepinephrine.