LOCAL CHOLINERGIC-ADRENERGIC INTERACTION: MECHANISM FOR THE BIPHASIC CHRONOTROPIC RESPONSE TO NERVE STIMULATION.

The secondary cardioinhibitory response to sympathetic nerve stimulation and the cardiostimulatory response to parasympathetic stimulation were investigated using preparations of isolated cat atria with parasympathetic (vagus) and sympathetic (poststellate ganglion) nerves intact. The effects of HC-3 administration and reserpinization on the responses to nerve stimulation were studied. Inhibition of the parasympathetic nervous system with hemicholinium (HC-3) abolished the negative chronotropic responses to both parasympathetic and sympathetic nerve stimulation. This suggests strongly the involvement of cholinergic fibers of the parasympathetic nervous system in these responses. HC-3 did not abolish the positive chronotropic response to sympathetic nerve stimulation at the time when the negative chronotropic response was inhibited. Pretreatment of animals with reserpine abolished both the positive chronotropic response to sympathetic nerve stimulation and the secondary positive chronotropic response to para. sympathetic nerve stimulation in atrial preparations made from these animals. The negative chronotropic response following sympathetic nerve stimulation was not abolished by reserpinization, but was inhibited by administration of HC-3 and vagus nerve stimulation. The involvement of cholinergic fibers of the parasympathetic nervous system in this response obviates the necessity of postulating cholinergic fibers in the cardiac sympathetic nerves. The ability of the cholinergic nerves to influence adrenergic nerve activity and of adrenergic nerves to influence cholinergic nerve activity has been demonstrated.