Skip to main content
Log in

Negative Inotropie von endogenem Acetylcholin beim Katzen- und Hühnerventrikelmyokard

Negative inotropic effects of endogenous acetylcholine on ventricular myocardium of cat and chicken

  • Published:
Pflügers Archiv Aims and scope Submit manuscript

Summary

The effect of endogenous acetylcholine (ACh) on the isometric force of contraction has been investigated on 40 papillary muscles of the cat right ventricle and on 20 strips of the chicken right ventricle. ACh was released from intramural cholinergic nerve endings by high voltage stimulation and simultaneous application of trains of stimuli during the absolute refractory period of the myocardium. In the pharmacologically untreated heart muscle the negative inotropic effect of sndogenous ACh was generally superimposed on the positive inotropic effect of simultaneously released catecholamines. During trains of high voltage stimuli, cat papillary muscles pretreated with reserpine showed a significant reduction in amplitude (average 19%) only if contractility had been increased by previous application of noradrenaline or isoprenaline. With guanethidine pretreatment high voltage stimulation reduced the amplitude significantly by 34%. In ventricular myocardium of chicken the negative inotropic effect of endogenous ACh was more impressive even in the absence of an increased contractility due to catecholamines. It is concluded from the following findings, that the negative inotropic substance is ACh: the negative inotropic effect was intensified by neostigmine and prevented by atropine; liquid, sampled from the bath during trains of high voltage stimuli was able to induce a contracture of frog rectus; under trains of high voltage stimuli the radio-activity in the perfusion liquid of preparations, pretreated with ratio-active ACh, was increased during the wash-out period. Moreover, the existence of cholinergic nerve fibers could be detected in cat papillary muscles as well as in chicken heart preparations by means of histochemical identification.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Literatur

  • Antoni, H., Rotmann, M.: Zum Mechanismus der negativ inotropen Acetylcholin-Wirkung auf das isolierte Froschmyokard. Pflügers Arch. ges. Physiol.300, 67 (1968).

    Google Scholar 

  • Bauereisen, E.: Die Bedeutung der Reizspannung und Reizdauer für die chronotrope Wirkung der extracardialen Nerven des Froschherzens. Z. Biol.100, 554 (1941).

    Google Scholar 

  • Blinks, J. R.: Field stimulation as a means of effecting the graded release of autonomic transmitters in isolated heart muscle. J. Pharmacol. exp. Ther.151, 221 (1966).

    Google Scholar 

  • Bolton, T. B.: Intramural nerves in the ventricular myocardium of the domestic fowl and other animals. Brit. J. Pharmacol.31, 253 (1967).

    Google Scholar 

  • Boyd, H., Chang, V., Rand, M. J.: The anticholinesterase activity of some antiadrenaline agents. Brit. J. Pharmacol.15, 525 (1960).

    Google Scholar 

  • Brady, A. J., Abbott, B. C., Mommaerts, W. F. H. M.: Inotropic effects of impulses applied during the contraction of cardiac muscle. J. gen. Physiol.44, 415 (1960).

    Google Scholar 

  • Callingham, B. A., Burgen, A. S. V.: The uptake of isoprenaline and noradrenaline by the perfused rat heart. Molec. Pharmacol.2, 37 (1966).

    Google Scholar 

  • Dagget, W. M., Nugent, G. C., Carr, P. W., Powers, P. C., Harada, Y.: Influence of vagal stimulation on ventricular contractility, O2 consumption and coronary flow. Amer. J. Physiol.212, 8 (1967).

    Google Scholar 

  • De Geest, H., Levy, M. N.: Negative inotropic effect of the vagus upon the canine ventricle. Science144, 1223 (1964)

    Google Scholar 

  • ——, Zieske, H., Lipman, R. J.: Depression of ventricular contractility by stimulation of the vagus nerves. Circulat. Res.17, 222 (1965).

    Google Scholar 

  • Dempsey, P. J., Cooper, T.: Ventricular cholinergic receptor systems: interaction with adrenergic systems. J. Pharmacol. exp. Ther.167, 282 (1969).

    Google Scholar 

  • Ehinger, B., Falck, B., Persson, H., Sporrong, B.: Adrenergic and cholinesterase-containing neurons of the heart. Histochemie16, 197 (1968).

    Google Scholar 

  • El-Badawi, A., Schenk, E. A.: Histochemical methods for separate, consecutive and simultaneous demonstration of acetylcholinesterase and norepinephrine in cryostat sections. J. Histochem. Cytochem.15, 580 (1967).

    Google Scholar 

  • Endoh, M., Hashimoto, K.: Pharmacological evidence of autonomic nerveactivities in canine papillary muscle. Amer. J. Physiol.218, 1459 (1970).

    Google Scholar 

  • Hirano, H., Ogawa, K.: Ultrastructural localization of cholinesterase activity in nerve endings in the guinea-pig heart. J. Electromicrosc.16, 313 (1967).

    Google Scholar 

  • ——: Ultracytochemical demonstration of cholinesterase activity in the atrium of the guinea-pig heart. Histochemie17, 49 (1969).

    Google Scholar 

  • Hoffman, B. F., Suckling, E. E.: Cardiac cellular potentials: Effect of vagal stimulation and acetylcholine. Amer. J. Physiol.173, 312 (1953).

    Google Scholar 

  • Hollenberg, M., Carriere, S., Barger, A. C.: Biphasic action of acetylcholine on ventricular myocardium. Circulat. Res.16, 527 (1965).

    Google Scholar 

  • Jacob, R., Kienzle, H. F., Sieber, G., Wille, E.: Catecholamine antagonism of exogenous and endogenous acetylcholine in the mammalian ventricular myocardium. Proc. physiol. Sci.9, 276 (1971).

    Google Scholar 

  • —, Miller, D. T., Gilmore, J. P.: Kontraktionskraft und Aktionspotential des Säuger-Ventrikelmyokards unter dem Einfluß geringer Acetylcholin-Konzentrationen. Pflügers Arch.316, R 14 (1970).

    Google Scholar 

  • ———: Antiadrenerge Effekte von Acetylcholin und ihre Bedeutung für Kontraktionskraft und Aktionspotential des Säugerventrikelmyokards. Ärztl. Forsch.25, 141 (1971).

    Google Scholar 

  • Jacobowitz, D., Cooper, T., Barner, H. B.: Histochemical and chemical studies of the localization of adrenergic and cholinergic nerves in normal and denervated cat hearts. Circulat. Res.20, 289 (1967).

    Google Scholar 

  • Janke, J., Fleckenstein, A., Jaedicke, W.: Hemmung der Isoproterenol-induzierten 45 Ca++-Netto-Aufnahme in das Ventrikelmyokard durch Ca++-antagonistische Hemmstoffe der elektro-mechanischen Koppelung (Isoptin=Verapramil, Iproveratril und Substanz D 600). Pflügers Arch.316, R 10 (1970).

    Google Scholar 

  • Karnovsky, M. J.: The localization of cholinesterase activity in rat cardiac muscle by electron microscopy. J. Cell Biol.23, 217 (1964).

    Google Scholar 

  • Kissling, G., Jacob, R., Peiper, U., Bauereisen E.: Inotrope Wirkungen des Nervus Vagus am Hundeventrikel in situ. Pflügers Arch.310, 64 (1970).

    Google Scholar 

  • Levy, M. N., Ng, M., Lipman, R. J., Zieske, H.: Vagus nerves and baroreceptor control of ventricular performance. Circulat. Res.18, 101 (1966).

    Google Scholar 

  • ——, Martin, P., Zieske, H.: Sympathetic and parasympathetic interaction upo the left ventricle of the dog. Circulat. Res.19, 5 (1966).

    Google Scholar 

  • —, Zieske, H.: Effect of enhanced contractility on the left ventricular response to vagus nerve stimulation in dogs. Circulat. Res.24, 303 (1969).

    Google Scholar 

  • Lieberman, M., Paes de Carvalho, A.: Effect of locally applied acetylcholine on the embryonic cardiac action potential. Experientia (Basel)23, 539 (1967).

    Google Scholar 

  • Löffelholz, K., Muscholl, E.: A muscarinic inhibition of the noradrenaline release evoked by postganglionic sympathetic nerve stimulation. Naunyn-Schmiedebergs Arch. Pharmak.265, 1 (1969).

    Google Scholar 

  • ——: Inhibition by parasympathetic nerve stimulation of the release of the adrenergic transmitter. Naunyn-Schmiedebergs Arch. Pharmak.267, 18 (1970).

    Google Scholar 

  • Meester, W. D., Hardman, H. F.: Blockade of the positive inotropic actions of epinephrine and theophylline by acetylcholine. J. Pharmacol. exp. Ther.158, 241 (1967).

    Google Scholar 

  • Murad, F., Chi, Y. M., Rall, T. W., Sutherland, E. W.: Adenyl cyclase. III. The effect of catecholamines and choline esters on the formation of adenosine 3′5-phosphate by preparations from cardiac muscle and liver. J. biol. Chem.237, 1233 (1962).

    Google Scholar 

  • Navaratnam, V., Lewis, P. R., Shute, C. C. D.: Effects of vagotomy on the cholinesterase content of the preganglionic innervation of the rat heart. J. Anat. (Lond.)103, 225 (1968).

    Google Scholar 

  • Nilsson, E., Sporrong, B.: Electron microscopic investigation of adrenergic and non adrenergic axons in the rabbit SA-node. Z. Zellforsch.111, 404 (1970).

    Google Scholar 

  • Pearse, A. G. E.: Histochemistry. Theoretical and applied, 2nd. Ed. London: Churchill 1960.

    Google Scholar 

  • Romeis, B.: Mikroskopische Technik, 16. Aufl. München-Wien: Oldenbourg 1968.

    Google Scholar 

  • Rothberger, C. J., Scherf, D.: Wirkt der Vagus auf die Kontraktionsstärke der Kammern des Säugetierherzens? Z. ges. exp. Med.71, 274 (1930).

    Google Scholar 

  • Rothschuh, K. E.: Vorkommen und Funktionen des Acetylcholins im Herzen. Klin. Wschr.32, 1 (1954).

    Google Scholar 

  • Sarnoff, S. J., Mitchell, J. H.: The control of the function of the heart. Handbook of physiology, circulation, Vol. I, p. 489. Washington D. C., 1962.

    Google Scholar 

  • Schaefer, H.: Central control of cardiac function. Physiol. Rev.40, Suppl. 4, 213 (1960).

    Google Scholar 

  • Schmidt, R. F.: Über die Acetylcholin-Empfindlichkeit verschiedener Herzabschnitte Naunyn-Schmiedebergs Arch. exp. Path. Pharmak.233, 531 (1958).

    Google Scholar 

  • Schütz, E.: Physiologie des Herzens. Hrsg. W. Trendelenburg und E. Schütz. Lehrbuch der Physiologie. Berlin-Göttingen-Heidelberg: Springer 1958.

    Google Scholar 

  • Tcheng, K. T.: Innervation du myocarde et du faisceau de HIS chez deux mammiféres, le mouton et le chat. Cardiologia (Basel)15, 227 (1950).

    Google Scholar 

  • Trautwein, W.: Elektrophysiologie der Herzmuskelfaser. Ergebn. Physiol.51, 131 (1961).

    Google Scholar 

  • Vincent, N. H., Ellis, S.: Inhibitory effect ofacetylcholine on glycogenolysis in the isolated guinea pig heart. J. Pharmacol. exp. Ther.139, 60 (1963).

    Google Scholar 

  • Vincenzi, F. F., West, T. C.: Release of autonomic mediators in cardiac tissue by direct subthreshold electrical stimulation. J. Pharmacol. exp. Ther.141, 185 (1963).

    Google Scholar 

  • Whalen, W. J., Fishman, N., Erickson, R.: Nature of the potentiating substance in cardiac muscle. Amer. J. Physiol.194, 573 (1958).

    Google Scholar 

  • Wille, E., Sieber, G., Jacob, R., Miller, D. T.: Effekte von Acetylcholin auf das Aktionspotential des isolierten Katzenpapillarmuskels bei adrenergisch gesteigerter Kontraktilität. (Zum Druck eingesandt).

Download references

Author information

Authors and Affiliations

Authors

Additional information

Ein Teil der Ergebnisse wurde bereits anläßlich der 38. Tagung der Deutschen Physiologischen Gesellschaft in Erlangen vom 29. 9. bis 2. 10. 1970 als vorläufige Mitteilung publiziert [vgl. Pflügers Arch.319, R 18 (1970)].

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kissling, G., Reutter, K., Sieber, G. et al. Negative Inotropie von endogenem Acetylcholin beim Katzen- und Hühnerventrikelmyokard. Pflugers Arch. 333, 35–50 (1972). https://doi.org/10.1007/BF00586040

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00586040

Key words

Navigation