title: Modifications by lidocaine and its N-dealkylated metabolites of the response of the isolated rabbit aorta to transmural electrical stimulation.
abstract: Contractile responses of rabbit aortic strips to transmural stimulation and to exogenously applied norepinephrine (NE), potassium chloride (KCl), and histamine were studied in the presence of lidocaine or its metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX). Lidocaine, 10(-4) and 5 x 10(-4) M, attenuated the contractile response to transmural stimulation, whereas MEGX, 2 x 10(-5) and 10(-4) M, potentiated, but 10(-4) M, potentiated the response to transmural stimulation. The suppression induced by lidocaine and MEGX was not reversed by excess calcium, 2.2 and 4.4 mM, but was partially reversed by cocaine, 3 x 10(-6) M. Lidoncaine, 5 x 10(-4) M, and MEGX, 2 x 10(-3) M, shifted the dose-response curve of NE to the right, whereas GX, 5 x 10(-4) M, shifted the curve to the left. The maximum tension developed by K+ was attenuated by lidocaine, 5 x 10(-4) M, MEGX, 5 x 10(-4) and 2 x 10(-3) M, and GX, 2 x 10(-3) M. It may be concluded that lidocaine attenuates the response to stimulation of sympathetic nerves innervating the arterial wall by interfering with the release of NE. In contrast, the metabolites, MEGX and GX, potentiate the response, possibly by increasing the release of NE. MEGX in high concentrations appears to have the same mechanism of inhibitory action as does lidocaine.
mesh_terms: D000478:Alkylation; D000818:Animals; D001013:Aorta, Thoracic; D001949:Bretylium Compounds / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D004558:Electric Stimulation; D008012:Lidocaine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits
chemical_list: D001949:Bretylium Compounds; D008012:Lidocaine; C001306:glycinexylidide; C001173:monoethylglycinexylidide; D003042:Cocaine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine; D010646:Phentolamine