Blockade of the nicotine-induced norepinephrine release by cocaine, phenoxybenzamine and desipramine

TLDR: It was concluded that the sympathomimetic action of nicotine on the pulmonary artery was mediated by the release of endogenous NE, and was not dependent on the initiation and propagation of action potentials in the axon.

Abstract: The effect of some drugs on the sympathomimetic action of nicotine was studied with the superfused spiral strip of the rabbit pulmonary artery. Nicotine or tranamural electrical stimulation evoked an increase in isometric tension and, in artery strips labeled with tritiated dl -norepinephrine (H3-NE), overflow of H3-NE into the superfusate. Treatment of the rabbit with reserpine prior to isolation of the artery eliminated such contraction. Tetrodotoxin and bretylium, in concentrations which rapidly abolished the contraction and H2- NE overflow evoked by tranamuralstimulation, failed to affect the response to nicotine. Phenoxybenzamine, cocaine and desipramine selectively inhibited the nicotine-induced contraction and overflow. It was concluded that the sympathomimetic action of nicotine on the pulmonary artery was mediated by the release of endogenous NE ; this release was not dependent on the initiation and propagation of action potentials in the axon. Since those agents which prevented the nicotine effect possess the common property of inhibiting the uptake of NE, the action of nicotine may require an intact NE uptake mechanism.