Summary
Conflicting results exist about the influence of cyclic N6-2′-O-dibutyryl-AMP (DB-c-AMP) on myocardial contractile force. The present study was designed to examine whether the positive inotropic action of DB-c-AMP is restricted to certain model preparations or whether it can be assumed to represent a more general effect of the drug. Therefore, the effects of DB-c-AMP on myocardial force and on various parameters of the isometric contraction curve were examined in isolated electrically driven (0.5–2Hz) ventricular and atrial preparations of several mammalian species (cat, rabbit, calf, sheep, rat and guinea-pig). The following results were obtained:
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1.
At concentrations above 3×10−4M, DB-c-AMP exerted concentrationdependent positive inotropic effects in all ventricular preparations studied. These effects were accompanied by increases in the rates of force development and relaxation and by decreases in time to peak force and relaxation time.
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2.
Positive inotropic responses to DB-c-AMP were also obtained in atrial preparations of cats, rabbits, calves, sheep and rats. In guinea-pig auricles, similar effects were seen when the preparations were treated with the phosphodiesterase inhibitor papaverine.
The results suggest that the positive inotropic action of DB-c-AMP is not restricted to certain model preparations and can be obtained in all cases under suitable experimental conditions.
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References
Ahrén, K., Hjalmarson, Å., Isaksson, O.: Inotropic and metabolic effects of dibutyryl cyclic adenosine 3′,5′-monophosphate in the perfused rat heart. Acta physiol. scand. 82, 79–90 (1971)
Bertelli, A., Bianchi, C., Beani, L.: Effects of AMP and cyclic AMP on the mechanical and electrical activity of isolated mammalian atria. Europ. J. Pharmacol. 19, 130–133 (1972)
Drummond, G. I., Hemmings, S. J.: Inotropic and chronotropic effects of dibutyryl cyclic AMP. In: Advances in cyclic nucleotide research. Eds.: P. Greengard, G. A. Robison, and R. Paoletti, Vol. I, pp. 307–316. New York: Raven Press 1972
Gartner, S. L., Vahouny, G. V.: Effects of epinephrine and cyclic 3′,5′-AMP on perfused rat hearts. Amer. J. Physiol. 222, 1121–1124 (1972)
Koch-Weser, J.: Effect of rate changes on strength and time course of contraction of papillary muscle. Amer. J. Physiol. 204, 451–457 (1963)
Kukovetz, W. R., Pöch, G.: Cardiostimulatory effects of cyclic 3′,5′-adenosine monophosphate and its acylated derivatives. Naunyn-Schmiedebergs Arch. Pharmak. 266, 236–254 (1970a)
Kukovetz, W. R., Pöch, G.: Inhibition of cyclic-3′,5′-nucleotide-phosphodiesterase as a possible mode of action of papaverine and similarly acting drugs. Naunyn-Schmiedebergs Arch. Pharmak. 267, 189–194 (1970b)
Meinertz, T., Nawrath, H., Scholz, H.: Über die positiv inotrope Wirkung von Dibutyryl-3′,5′-AMP an isolierten Rattenvorhöfen. Pflügers Arch. 333, 197–212 (1972)
Meinertz, T., Nawrath, H., Scholz, H.: Adrenaline, DB-c-AMP and myocardial 45Ca exchange. Comparative studies in rat and guinea-pig auricles. Naunyn-Schmiedeberg's Arch. Pharmacol. 279, 313–325 (1973a)
Meinertz, T., Nawrath, H., Scholz, H.: Influence of cyclization and acyl substitution on the inotropic effects of adenine nucleotides. Naunyn-Schmiedeberg's Arch. Pharmacol. 278, 165–178 (1973b)
Meinertz, T., Nawrath, H., Schmitz, W., Scholz, H.: Failure of reserpinization to decrease the positive inotropic effect of dibutyryl cyclic AMP. Res. Comm. Chem. Path. Pharmacol. 6, 383–390 (1973c)
Øye, I., Langslet, A.: The role of cyclic AMP in the inotropic response to isoprenaline and glucagon. In: Advances in cyclic nucleotide research. Eds.: P. Greengard, G. A. Robison, and R. Paoletti, Vol. I., pp. 291–300. New York: Raven Press 1972
Pöch, G., Juan, H., Kukovetz, W. R.: Influence of cardio-and vasoactive substances on phosphodiesterase activity. Naunyn-Schmiedebergs Arch. Pharmak. 264, 293–294 (1969)
Reiter, M., Schöber, H. G.: Die positiv inotrope Adrenalinwirkung auf den Meer-schweinchen-Papillarmuskel bei Variation der äußeren Calcium-und Natrium-konzentration. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 250, 9–20 (1965)
Reiter, M., Stickel, F. J.: Der Einfluß der Kontraktionsfrequenz auf das Aktions-potential des Meerschweinchen-Papillarmuskels. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 260, 342–365 (1968)
Robison, G. A., Butcher, R. W., Øye, L., Morgan, H. E., Sutherland, E. W.: The effect of epinephrine on adenosine 3′,5′-phosphate levels in the isolated perfused rat heart. Molec. Pharmacol. 1, 168–177 (1965)
Robison, G. A., Butcher, R. W., Sutherland, E. W.: Cyclic AMP. New York-London: Academic Press 1971
Sheppard, H., Wiggan, G., Tsien, W. H.: Structure-activity relationships for inhibitors of phosphodiesterase from erythrocytes and other tissues. In: Advances in cyclic nucleotide research. Eds.: P. Greengard, G. A. Robison, and R. Paoletti, Vol. I, pp. 103–112. New York: Raven Press 1972
Skelton, C. L., Levey, G. S., Epstein, S. E.: Positive inotropic effects of dibutyryl cyclic adenosine 3′,5′-monophosphate. Circulat. Res. 26, 35–43 (1970)
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Meinertz, T., Nawrath, H., Scholz, H. et al. Effect of DB-c-AMP on mechanical characteristics of ventricular and atrial preparations of several mammalian species. Naunyn-Schmiedeberg's Arch. Pharmacol. 282, 143–153 (1974). https://doi.org/10.1007/BF00499029
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DOI: https://doi.org/10.1007/BF00499029