Effects of amide-linked local anesthetics on adrenergic neuroeffector junction in cutaneous veins of dog

SM Muldoon, TJ Verbeuren and PM Vanhoutte

When changes in isometric tension of helical strips of dog saphenous veins were recorded, etidocaine caused a dose-dependent depression of the contractile responses to nerve stimulation, norepinephrine and K+. The response to nerve stimulation was significantly more depressed than that to exogenous norepinephrine. Similar results were obtained with lidocaine. In preparations incubated in solutions containing 3H- norepinephrine and mounted for superfusion and isometric tension recording, etidocaine depressed the contractions and diminished the release of 3H-norepinephrine evoked by nerve stimulation. Thus, in addition to an inhibitory effect on the responses of smooth muscle cells, amide-linked local anesthetic agents such as etidocaine depress adrenergic neurotransmission in the blood vessel wall, which helps explain their vasodilator properties in the intact organism. In unstimulated preparations and during contractions caused by K+, etidocaine increased the efflux of 3H-norepinephrine and deaminated metabolites. After incubation with the monamine oxidase inhibitor, pargyline, etidocaine augmented markedly the efflux of 3H- norepinephrine. During responses to tyramine, it augmented the release of 3H-norepinephrine more than the efflux of deaminated compounds. This suggests that etidocaine augments the leakage of norepinephrine out of the storage vesicles, making more catecholamines available for intraneuronal deamination.

Volume 196, Issue 3, pp. 723-736, 03/01/1976
Copyright © 1976 by American Society for Pharmacology and Experimental Therapeutics

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