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Cardiac contractile and metabolic effects mediated via the myocardial H2-receptor adenylate cyclase system

Characterization of Two New Specific H2-Receptor Agonists, Impromidine and Dimaprit, in the Guinea Pig and Human Myocardium

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Research in Experimental Medicine

Summary

The present study characterizes myocardial effects of two new histaminergic H2-receptor specific compounds, impromidine, and dimaprit, on cardiac contractile and metabolic parameters of the guinea pig heart and human papillary muscle in comparison to the well-known effects of catecholamines. Impromidine and dimaprit produced a dose-dependent stimulation of the right and left ventricular contractile force in the isolated perfused biventricular catheterized guinea pig heart with maximal stimulation rates equal to those of isoproterenol. Hemodynamic equieffective doses of isoproterenol (2.8 × 10−9 mol/l), histamine (1.1 × 10−5 mol/l), impromidine (4.6 × 10−7 mol/l), and dimaprit (8.5 × 10−6 mol/l) induced nearly identical increases in tissue concentrations of c-AMP. All compounds dose-dependently enhanced the activity of the myocardial adenylate cyclase with very similar KA-values in a particulate sarcolemmal membrane preparation of both guinea pig ventricles and human papillary muscles. No effect of either compound was seen on cardiac phosphodiesterase activity. Selective administration of theβ 1-blocking agent metoprolol and the H2-receptor antagonist cimetidine clearly discriminates two independent receptors linked to the sarcolemmal adenylate cyclase system in the guinea pig and human myocardium. This is further supported by results obtained fromβ-receptor-binding studies in which an interference of impromidine and dimaprit with the stereospecific binding of (−)[3H]-dihydroalprenolol to cardiacβ-receptors could be definitely excluded. The possible therapeutic role of both H2-agonists on the non-ischemic, surviving myocardium, which is transiently refractory toβ-adrenergic stimulation by catecholamines after myocardial infarction, will be discussed.

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Authors and Affiliations

  1. 1st Dept. of Internal Medicine, Division of Cardiology and Circulation, Technical University of Munich, Ismaninger Str. 22, D-8000, Munich 80, Federal Republic of Germany

    G. Baumann, St. B. Felix, C. D. Heidecke, G. Rieß, L. Ludwig, U. Loher & H. Blömer

  2. Dept. of Physiology, University of Munich, Pettenkofer Str. 12, D-8000, Munich 2, Federal Republic of Germany

    J. Schrader

  3. Institute for Experimental Surgery, Klinikum rechts der Isar, Ismaninger Str. 22, D-8000, Munich 80, Federal Republic of Germany

    W. D. Erhardt

  4. Deutsches Herzzentrum München, Lothstr. 11, D-8000, Munich 2, Federal Republic of Germany

    F. Sebening (Head of the Department of Cardiovascular Surgery)

Authors
  1. G. Baumann
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  2. St. B. Felix
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  3. J. Schrader
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  4. C. D. Heidecke
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  5. G. Rieß
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  6. W. D. Erhardt
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  7. L. Ludwig
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  8. U. Loher
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  9. F. Sebening
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  10. H. Blömer
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Additional information

Results presented in this study are part of the doctoral thesis by Mr. St. B. Felix

Supported by the Deutsche Forschungsgemeinschaft (DFG), grant no. Ba 666/1

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Baumann, G., Felix, S.B., Schrader, J. et al. Cardiac contractile and metabolic effects mediated via the myocardial H2-receptor adenylate cyclase system. Res. Exp. Med. 179, 81–98 (1981). https://doi.org/10.1007/BF01852128

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  • DOI: https://doi.org/10.1007/BF01852128

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