Premium
Trimebutine maleate relaxes the isolated rat thoracic aorta: The role of nitric oxide and L‐type calcium channels
Author(s) -
Kadioglu Mine,
Kaya Yasar Yesim,
Barut Elif Nur,
Engin Seckin
Publication year - 2019
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.13051
Subject(s) - endothelium , phenylephrine , chemistry , carbachol , aorta , thoracic aorta , bay k8644 , contractility , nitric oxide , voltage dependent calcium channel , medicine , vasoconstriction , pharmacology , endocrinology , calcium , stimulation , blood pressure
Summary Trimebutine maleate ( TMB ), a widely prescribed drug for functional gastrointestinal disorders, has been reported to regulate smooth muscle contractility by modulating multiple ion channel activities in the gastrointestinal tract. However, its action on isolated aorta has not yet been reported. The aim of the present study was to evaluate in vitro vasorelaxant properties and the underlying pharmacological mechanisms of TMB in isolated rat thoracic aortic rings. Vascular activity experiments were performed on thoracic aorta isolated from Sprague‐Dawley rats in vitro, including endothelium‐intact and endothelium‐denuded aortic rings. TMB (10 −10 ‐10 −5 mol/L) induced relaxation in endothelium‐intact aortic rings precontracted by phenylephrine with a potency similar to that of carbachol. TMB ‐induced relaxation was not altered by glibenclamide and atropine in endothelium‐intact aortic rings. However, L‐ NAME and endothelium denudation significantly reduced but not completely reversed the vasorelaxant effect of TMB . Also, TMB ‐induced relaxation wasn't affected by diclofenac in endothelium‐intact aortic rings. TMB at 10 −5 mol/L significantly reduced the CaCl 2 ‐induced contractions in endothelium‐intact aortic rings stimulated with KC l, but not stimulated with phenylephrine under Ca 2+ free conditions. Moreover, TMB at 10 −5 mol/L effectively attenuated Bay‐K8644‐induced contractions in aortic rings. These results suggest that TMB ‐induced relaxation was mediated by both endothelium‐dependent and endothelium‐independent manner in isolated rat thoracic aorta. The mechanism of TMB ‐induced relaxation at low concentrations is partially related to NO ‐ and endothelium‐dependent but unrelated to prostanoids formation. However, inhibition of Ca 2+ influx through voltage‐operated calcium channels and L‐type Ca 2+ channel blocking effect appears to be involved in the mechanism of vasorelaxant effect of TMB at high concentrations.