The differential effect of calcium antagonists on the positive inotropic effects induced by calcium and monensin in cardiac preparations of rats and guinea-pigs.
It was the aim of the present study to gain more insight into the role of extracellular calcium and of calcium from intracellular sources in the development of contractile force in the mammalian heart. In rat Langendorff hearts the effect of nifedipine, verapamil, diltiazem, bepridil and lidoflazine as well as of the intracellularly acting calcium antagonists ryanodine and TMB-8 on the increase of the left ventricular pressure induced by calcium and the sodium ionophore monensin, respectively, was studied. In rat and guinea-pig papillary muscles the influence of nifedipine, ryanodine and lidoflazine on the effect of monensin on the force of contraction was evaluated. Calcium and monensin concentration-dependently increased the left ventricular pressure in rat Langendorff hearts. The calcium-induced effect was characterized by a sharp initial rise of the left ventricular pressure which stabilized at a lower level while monensin elicited a gradual rise of the left ventricular pressure. Nifedipine, verapamil and diltiazem, applied at the EC50 and the EC80 for the reduction of the left ventricular pressure under control conditions, shifted the concentration-response curves for calcium and monensin into the right. Ryanodine, TMB-8, lidoflazine and bepridil, applied at the EC50, displaced the concentration-response curves for calcium and monensin to the right but reduced the maximal increase of the left ventricular pressure. At the EC80, these drugs almost completely abolished the positive inotropic effects elicited by calcium and monensin, respectively. In rat papillary muscles monensin did not influence the basal force of contraction. A clear positive inotropic effect was only observed in the presence of nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)
Hugtenburg
J G
JG
Department of Pharmacotherapy/Pharmacology, Faculty of Medicine, University of Amsterdam, The Netherlands.
Mathy
M J
MJ
Beckeringh
J J
JJ
van Zwieten
P A
PA
D000818:Animals; D015764:Bepridil / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006352:Heart Ventricles / Q000187:drug effects; D008013:Lidoflazine / Q000494:pharmacology; D008297:Male; D008985:Monensin / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012433:Ryanodine / Q000494:pharmacology; D013268:Stimulation, Chemical; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D012433:Ryanodine; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D015764:Bepridil; D008985:Monensin; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D008013:Lidoflazine; D002118:Calcium