Attenuation of long-lasting effects of sympathetic stimulation after repeated stimulation.

Abstract

Neuropeptide Y (NPY) is stored with norepinephrine in sympathetic nerves throughout the cardiovascular system and is released during activation of the sympathetic nervous system in humans and other animals. After stimulation of the cardiac sympathetic nerves in anesthetized dogs, the action of the vagus nerve on heart rate is attenuated for a prolonged period. This attenuation of cardiac vagal action is also seen after injection of NPY. Both sympathetic stimulation and exogenous NPY inhibit cardiac vagal effects by acting on postganglionic vagal nerves. Because the supply of neuropeptides to nerve terminals is by axonal transport, it might be expected that repeated stimulation of cardiac sympathetic nerves would deplete the sympathetic neural factor, proposed to be NPY. In all 11 dogs of this study, repeated episodes of stimulating the cardiac sympathetic nerve (16 Hz for 1 minute each) had a diminishing effect in attenuating cardiac vagal action. However, the episodes of sympathetic stimulation did not show diminishing effectiveness in increasing heart rate. Exogenous NPY had similar inhibitory effects on vagal action whether given at the beginning or the end of the episodes of sympathetic stimulation. Transmural stimulation of sympathetic nerves around rabbit ear arteries produced effects that are also mimicked by NPY. These are prolonged potentiation of contractions evoked by injection of norepinephrine or by brief bursts of transmural stimulation. Repeated stimulations in this case also had diminishing abilities to evoke such potentiations. Both sets of observations are consistent with repeated stimulation of sympathetic nerves causing depletion of a nonadrenergic transmitter, possibly NPY.