[Differential regulation of the release of norepinephrine and neuropeptide Y]

Abstract

The release of catecholamines and their co-neurotransmitter neuropeptide Y was investigated in conscious dogs with neurogenic arterial hypertension elicited by sinoaortic denervation. One month after denervation, an elevation of catecholamine levels (measured by HPLC) without elevation of neuropeptide Y levels in plasma (evaluated by RIA) has been found. This dissociation could be explained by a transient release of neuropeptide Y during the first weeks after surgery; a depletion of neuronal neuropeptide Y due to the permanent sympathetic stimulation; or an insufficient increase in sympathetic tone. To test these three hypotheses, we investigated the time courses of catecholamine and neuropeptide Y levels in arterial plasma during the first five weeks after sinoaortic denervation; and the responses to yohimbine (an alpha 2 antagonist which enhances transmitter release). Resting neuropeptide Y levels in plasma remained normal during the first five weeks after sinoaortic denervation. In normal dogs, a high dose of yohimbine (0.5 mg/kg i.v.) elevated both catecholamine (6-fold) and neuropeptide Y levels (1.5-fold), whereas a lower dose (0.05 mg/kg i.v.) induced a two fold elevation of catecholamine levels without changing neuropeptide Y concentrations. In sinoaortically denervated dogs, yohimbine elicited elevation of both catecholamines and neuropeptide Y whatever the dose used. Thus, neurogenic arterial hypertension in dogs seams to involve catecholamines but not neuropeptide Y. Moreover, the present work suggests that a high level of sympathetic stimulation is required for a co-release of catecholamines and neuropeptide Y.