Inhibition of iloprost of the contractile effect of noradrenaline in mesenteric artery rings: evidence for a possible calcium-dependent mechanism.
Iloprost caused a concentration-dependent decrease in the response to noradrenaline in the rabbit isolated endothelium denuded rings from superior mesenteric artery but not thoracic aorta. Similar inhibition was obtained by verapamil using identical concentrations. In Ca(2+)-free EGTA containing medium noradrenaline both at lower and higher concentrations elicited a reduced contractile response and further addition of Ca2+ (2.5 mM) to the medium produced a second contraction in both mesenteric artery and aortic rings which was significantly and equally inhibited by iloprost and verapamil using identical concentrations in mesenteric artery but not in aortic rings. Prior addition of iloprost to the medium did not protect the inhibitory effect of phenoxybenzamine against noradrenaline-induced contraction. These results were taken as an evidence for the possible Ca2+ entry reducing effect of iloprost in mesenteric artery but not thoracic aorta. These results were also taken as an indirect evidence supporting the hypothesis that increased synthesis of prostacyclin by noradrenaline in the vascular wall may inhibit the contractile effect of the agonist by a (-) feedback mechanism mediated by Ca2+ entry into the vascular smooth muscle.
Demirel
E
E
Department of Pharmacology, Faculty of Medicine, University of Ankara, Turkey.
Türker
R K
RK
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000502:physiology*; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D016285:Iloprost / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology*; D010643:Phenoxybenzamine / Q000494:pharmacology; D011817:Rabbits; D011941:Receptors, Adrenergic / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D011941:Receptors, Adrenergic; D010643:Phenoxybenzamine; D014700:Verapamil; D016285:Iloprost; D002118:Calcium; D009638:Norepinephrine