title: Effect of isomazole on the responsiveness to calcium of the contractile elements in skinned cardiac muscle fibres of various species.
abstract: We report here that the new cardiotonic agent isomazole increases the Ca2+ responsiveness of skinned myocardial fibres from different species. Isomazole (0.01-1 mM) increased the half-maximal, Ca2+-activated force development in atrial fibres from humans and in ventricular fibres from pigs, monkeys, guinea-pigs and rats in a concentration-dependent manner. The maximal force development was also increased in fibres from all species except pig. Isomazole shifted force-calcium curves to the left and enhanced maximal force as demonstrated for guinea-pig and human fibres, indicating increases in both calcium sensitivity and maximum force-generating capability of the contractile apparatus. In guinea-pig tissue, the concentration dependence for the activation of skinned fibres was similar to that for the positive inotropic effect in papillary muscle. These results suggest a direct effect of isomazole on contractile proteins, but the degree to which this effect contributes to the overall positive inotropic action of isomazole remains to be determined.
authors.affiliation: Department of Pharmacology, E. Merck, Darmstadt, F.R.G.
authors.forename: I
authors.initials: I
authors.lastname: Lues
authors.forename: R
authors.initials: R
authors.lastname: Siegel
authors.forename: J
authors.initials: J
authors.lastname: Harting
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008252:Macaca fascicularis; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013552:Swine
chemical_list: D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; C029758:sulmazole; D002118:Calcium