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Negative inotropic effect of vanadate in ventricular myocardium in the presence of 3-isobutyl-1-methylxanthine or isoprenaline

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Summary

The influence of a low concentration of 3-isobutyl-1-methylxanthine (IBMX; 5μmol l−1) on the positive inotropic effect of vanadate (NH4VO3; 10–1,000 μmol l−1) and isoprenaline (ISO; 0.1–300 nmol l−1) was studied in electrically driven (frequency 1 Hz) papillary muscles isolated from guinea pigs. Furthermore the influence of maximally effective concentrations of IBMX (100μmol l−1), ISO (100nmol l−1) and dihydro-ouabain (DHO; 70μmol l−1) on the inotropic effect of NH4VO3 was investigated.

  1. 1.

    IBMX (5μmol l−1) shifted the concentrationresponse curve for ISO to the left (EC50-ratio 2.4). In contrast, the positive inotropic effect of NH4VO3 (mean EC50 81.7μmol l−1) was not influenced by IBMX at this concentration.

  2. 2.

    In the presence of high concentrations of IBMX or ISO, NH4VO3 exerted a concentration-dependent (10–1,000μmol l−1) atropine-insensitive negative inotropic effect with mean EC50 values of 40.1 μmol l−1 and 73.0μmol l−1, respectively.

  3. 3.

    In the presence of the maximally effective concentration of DHO, NH4VO3 had no effect on force of contraction, i.e. it neither further increased nor reduced the DHO-induced positive inotropic effect.

  4. 4.

    The negative inotropic effect of NH4VO3 in the presence of IBMX or ISO in guinea-pig papillary muscles was not accompanied by a shortening of the action potential.

  5. 5.

    From the failure of IBMX (5μmol l−1) to enhance the positive inotropic effect of NH4VO3 it is concluded that the recently described small increase in c-AMP, which accompanies the NH4VO3-produced increase in force of contraction in intact papillary muscles, is not of major importance in mediating the agent's positive inotropic effect.

  6. 6.

    The mechanism of the negative inotropic effect of NH4VO3 in the presence of high concentrations of IBMX or ISO remains obscure. Apparently, it is not due to a shortening of the action potential. A stimulation of muscarinic cholinergic receptors is also unlikely although there are obvious similarities between the negative inotropic effect of NH4VO3 and that of acetylcholine described under similar conditions in ventricular heart muscle preparations. Interestingly, all drugs hitherto found capable of evoking a negative inotropic effect of vanadate in ventricular tissue are well known to increase myocardial c-AMP levels.

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Authors and Affiliations

  1. Abteilung III (Biochemische Pharmakologie), Institut für Pharmakologie und Toxikologie, Medizinische Hochschule Hannover, Karl-Wiechert-Allee 9, D-3000, Hannover 61, Federal Republic of Germany

    Reinhard Brückner, Wilhelm Schmitz, Hasso Scholz & Arno Schumacher

  2. Medizinische Klinik I, Klinikum Großhadern, Universität München, Marchioninistraße 15, D-8000, München 70, Federal Republic of Germany

    Erland Erdmann, Wolfgang Krawietz & Karl Werdan

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  1. Reinhard Brückner
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  2. Wilhelm Schmitz
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  3. Hasso Scholz
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  4. Arno Schumacher
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  5. Erland Erdmann
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  6. Wolfgang Krawietz
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Brückner, R., Schmitz, W., Scholz, H. et al. Negative inotropic effect of vanadate in ventricular myocardium in the presence of 3-isobutyl-1-methylxanthine or isoprenaline. Naunyn-Schmiedeberg's Arch. Pharmacol. 315, 147–153 (1980). https://doi.org/10.1007/BF00499257

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  • DOI: https://doi.org/10.1007/BF00499257

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