Summary
-
1.
The influence of (+)-propranolol, 10−6 to 4×10−5 mol/l, upon the positive inotropic effect of dihydro-ouabain was studied on guinea-pig papillary muscle. At 1 Hz, negative inotropically effective concentrations of (+)-propranolol decreased the inotropic effectiveness of the glycoside.
-
2.
For equivalent diminution of the basal force of contraction, either by reduction of stimulation frequency or by increasing concentrations of (+)-propranolol, a similar decrease in the inotropic effectiveness of dihydro-ouabain was observed. In contrast, reduction of [Ca2+]0 had almost no effect on the effectiveness of the glycoside.
-
3.
The inhibitory effect of (+)-propranolol on the inotropic effectiveness of dihydro-ouabain declined with reduction of stimulation frequency. At any stimulation frequency tested, the inhibitory effect of (+)-propranolol was proportional to the effect of a reduction of that particular frequency to the rested-state condition in the absence of (+)-propranolol.
-
4.
The results are consistent with the hypothesis that the inhibition of the excitation-coupled sodium influx by (+)-propranolol is the cause of its inhibiting effect on the effectiveness of dihydro-ouabain.
Similar content being viewed by others
References
Balzer, H.: The effect of quinidine and drugs with quinidine-like action (propranolol, verapamil and tetracaine) on the calcium transport system in isolated sarcoplasmic reticulum vesicles of rabbit skeletal muscle. Naunyn-Schmiedeberg's Arch. Pharmacol. 274, 256–272 (1972)
Ban, T.: A kinetic study of effects of propranolol and N-propylajmaline on the rate of rise of action potential in guinea pig papillary muscles. Japan. J. Pharmacol. 27, 865–880 (1977)
Blinks, J. R., Koch-Weser, J.: Analysis of the effects of changes in rate and rhythm upon myocardial contractility. J. Pharmacol. Exp. Ther. 134, 373–389 (1961)
Coltart, D. J., Meldrum, S. J.: The effect of racemic propranolol, dextro-propranolol, and racemic practolol on the human and canine cardiac transmembrane action potential. (Beta blockade and the cardiac action potential. Arch. int. Pharmacodyn. 192, 188–197 (1971)
Davis, L. D., Temte, J. V.: Effects of propranolol on the transmembrane potentials of ventricular muscle and Purkinje fibers of the dog. Circulat. Res. 22, 661–677 (1968)
Dohadwalla, A. N., Freedberg, A. S., Vaughan Williams, E. M.: The relevance of β-receptor blockade to ouabain-induced arrhythmias. Br. J. Pharmacol. 36, 257–267 (1969)
Ebner, F., Reiter, M.: The inhibition of the positive inotropic effect of dihydro-ouabain by propranolol. Naunyn-Schmiedeberg's Arch. Pharmacol. 294, R 19 (1976)
Ebner, F., Reiter, M.: The dependence on contraction frequency of the positive inotropic effect of dihydro-ouabain. Naunyn-Schmiedeberg's Arch. Pharmacol. 300, 1–9 (1977)
Ebner, F., Reiter, M.: The alteration by propranolol of the inotropic and bathmotropic effects of dihydro-ouabain on guinea-pig papillary muscle. Naunyn-Schmiedeberg's Arch. Pharmacol. 307, 99–104 (1979)
Josephson, I., Sperelakis, N.: Ouabain blockade of inward slow current in cardiac muscle. J. Mol. Cell. Card. 9, 409–418 (1977)
Köhler, H.-W.: On-line-Datenaufnahme and real-time-Auswertung von isometrischen Kontraktionskurven des Herzmuskels mit Hilfe eines PDP-12-Computers. Arzneim.-Forsch. (Drug Res.) 24, 815–819 (1974)
Morales-Aguilerá, A., Vaughan Williams, E. M.: The effects on cardiac muscle of β-receptor antagonists in relation to their activity as local anaesthetics. Br. J. Pharmacol. 24, 332–338 (1965)
Pollen, D. W., Scott, A. C., Wallace, W. F. M.: A comparison of the direct effects and adrenergic blocking activity of d/l-and d-propranolol on the electrical and mechanical behaviour of isolated frog ventricle. Cardiovasc. Res. 3, 7–13 (1969)
Porzig, H.: Comparative study of the effects of propranolol and tetracaine on cation movements in resealed human red cell ghosts. J. Physiol. (Lond.) 249, 27–49 (1975)
Quadbeck, J., Reiter, M.: Adrenoceptors in cardiac ventricular muscle and changes in duration of action potential caused by noradrenaline and isoprenaline. Naunyn-Schmiedeberg's Arch. Pharmacol. 288, 403–414 (1975)
Reiter, M.: Die Untersuchung inotrop wirkender Substanzen. In: Festschrift 75 Jahre Hommel, pp. 480–484. Zürich: Hommel 1965
Scales, B., McIntosh, D. A. D.: Effects of propranolol and its optical isomers on the radiocalcium uptake and the adenosine triphosphateses of skeletal and cardiac sarcoplasmic reticulum fractions (SRF). J. Pharmacol. exp. Ther. 160, 261–267 (1968)
Tarr, M., Luckstead, E. F., Jurewicz, P. A., Haas, H. G.: Effect of propranolol on the fast inward sodium current in frog atrial muscle. J. Pharmacol. exp. Ther. 184, 599–610 (1973)
Temple, D. M., Hasselbach, W., Makinose, M.: The inhibition by β-adrenoceptor blocking agents of calcium uptake into and efflux from isolated sarcoplasmic vesicles. Naunyn-Schmiedeberg's Arch. Pharmacol. 282, 187–194 (1974)
Tritthart, H., Fleckenstein, B., Fleckenstein, A.: Some fundamental actions of antiarrhythmic drugs on the excitability and the contractility of single myocardial fibers. Naunyn-Schmiedeberg's Arch. Pharmacol. 269, 212–219 (1971)
Wu, C. H., Narahashi, T.: Mechanusm of action of propranolol on squid axon membranes. J. Pharmacol. exp. Ther. 184, 155–162 (1973)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ebner, F., Reiter, M. The influence of (+)-propranolol on the inotropic effect of dihydro-ouabain in relation to stimulation frequency. Naunyn-Schmiedeberg's Arch. Pharmacol. 307, 105–113 (1979). https://doi.org/10.1007/BF00498451
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00498451