Low dose verapamil and nitroprusside distinguish tonic from cholinergic- induced contractions in in vivo feline lower esophageal sphincter

DA Katzka, JC Reynolds, AD King and S Cohen

Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia.

Although in vitro studies suggest that cholinergic induced contractions and spontaneous tone are mediated by two different cellular pathways, this has not been shown in vivo. The purpose of this study was to distinguish these types of contractions in the feline lower esophageal sphincter (LES) through use of i.v. selective pharmacologic antagonists. Continuous infusion of the calcium channel antagonist verapamil (16-128 micrograms/kg/min) caused a dose-dependent inhibition of bethanechol induced and tonic pressure change. At 32.0 micrograms/kg/min, verapamil produced significantly greater inhibition of bethanechol induced contractions when compared with inhibition of basal LES tone (57.4 versus 4.8%, P less than .02, n = 5). Verapamil also caused a parallel decrease in LES spike activity associated with bethanechol induced contractions. In contrast, lower doses of nitroprusside (0.5 micrograms/kg/min) inhibited LES tone by over 50% (50.6 +/- 21.8%) yet had no significant effect (16.8 +/- 23.4%) on bethanechol induced contractions. Also, inhibition of basal LES tone correlated poorly with its effect on associated spike activity. It is concluded that in the in vivo feline LES, spike dependent cholinergic contractions can be distinguished from LES tone by the use of low dose verapamil and nitroprusside, respectively. This selective inhibition suggests that two cellular mechanisms mediate LES contractions and that these pathways can be distinguished pharmacologically in vivo.

Volume 256, Issue 1, pp. 189-193, 01/01/1991
Copyright © 1991 by American Society for Pharmacology and Experimental Therapeutics