PMID: 9420644Mar 1, 1995Paper

Effects of a novel cardiotonic agent, Org 9731, on force and aequorin light transients in intact ventricular myocardium of the dog: involvement of a cyclic AMP-mediated mechanism and myofibrillar responsiveness to Ca2+ ions

Journal of Cardiac Failure
Y Kawabata, M Endoh

Abstract

The action of a novel cardiotonic agent, Org 9731 (4-fluoro-N-hydroxy-5, 6-dimethoxy-benzo[b]thiophene-2-carboximidamide methanesulphonate), on intracellular aequorin light transients and isometric contractions was investigated in ventricular trabeculae isolated from dogs. The positive inotropic effect of Org 9731 at 3 microM and higher (up to 0.1 mM) was associated with an increase in the amplitude of the intracellular Ca2+ transient, but the effect of the compound at 0.3 and 1 mM was accompanied by a decrease of the transient. The maximum inotropic response to Org 9731 was approximately 70% of the maximum response to isoproterenol, while the maximum increase in the amplitude of Ca2+ transients produced by Org 9731 was about 30% of the maximum increase induced by isoproterenol. The duration of isometric contractions was prolonged by Org 9731 at 0.3 and 1 mM, with accompanying prolongation of the duration of light transients. The concentration-response curve for the positive inotropic effect of Org 9731 was markedly shifted by carbachol (3 microM), being moved to the right and downward, and the maximum response to Org 9731 was about 10% of that to isoproterenol in the presence of carbachol. Carbachol abolished the increase in t...Continue Reading

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Citations

Jun 27, 2006·Journal of Pharmacological Sciences·Masao Endoh

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