Effects of intense antecedent sympathetic stimulation on sympathetic neurotransmission in the heart.

We studied the effects of intense sympathetic stimulation on the chronotropic responses of the heart to subsequent test stimulations of the cardiac autonomic nerves in dogs anesthetized with alpha-chloralose. Such intense sympathetic stimulations (which we refer to as "release stimulations") are known to release neuropeptide Y as well as norepinephrine. The changes in cardiac cycle length evoked by vagal and sympathetic test stimulations were progressively more attenuated as we increased the frequency and duration of the antecedent sympathetic release stimulations. We found that 2.5 minutes after a maximal release stimulation (30 Hz for 5 minutes), the mean +/- SEM chronotropic responses to the vagal and sympathetic test stimulations were diminished to 36.5 +/- 1.6% and 54.7 +/- 1.3% respectively, of the prestimulation responses. The mean times for the chronotropic responses to the vagal and sympathetic test stimulations to recover to their control values were 52.0 +/- 1.3 and 63.2 +/- 2.9 minutes, respectively. This enduring effect suggests the action of a neuropeptide, such as neuropeptide Y. Phentolamine potentiated the inhibitory effects of the sympathetic release stimulations. The chronotropic responses to isoproterenol infusions were not affected appreciably by antecedent sympathetic release stimulation. We conclude, therefore, that the inhibitory effects of antecedent sympathetic release stimulation on cardiac sympathetic neurotransmission are mediated prejunctionally, probably via an inhibition of the neuronal release of norepinephrine by neuropeptide Y.