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Wirkung von Angiotensin auf Funktion und Noradrenalinabgabe isolierter Kaninchenherzen in Ruhe und bei Sympathicusreizung

Effects of angiotensin on the function of isolated rabbit hearts and on noradrenaline release at rest and during sympathetic nerve stimulation

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Summary

  1. 1.

    The influence of angiotensin on the isolated rabbit heart perfused at constant pressure or constant flow was investigated at rest and during electrical stimulation of the postganglionic sympathetic nerves.

  2. 2.

    In low concentrations (32–100ng/min or 1.4–5.3 ng/ml) angiotensin had considerable positive inotropic effects, while its chronotropic effects were weak and variable. High concentrations decreased the rate of beat, and an increase in the height of contraction was preceded by a transient phase of inhibition. In hearts perfused at constant pressure, angiotensin diminished coronary flow. The positive inotropic effect of angiotensin was not accompanied by the appearance of increased amounts of noradrenaline in the venous effluent.

  3. 3.

    Angiotensin caused a dose-dependent increase in the output of noradrenaline induced by sympathetic nerve stimulation. The peptide was most potent in hearts perfused at constant flow; the threshhold dose of angiotensin for this procedure was 3.2 ng/min (128 pg/ml), and maximal effects (i.e., an increase by 81%) were observed with 32 ng/min (1.28 ng/ml). Doses about three times higher were required to obtain similar effects in hearts perfused at constant pressure. The reduction of coronary flow as seen under these conditions may be responsible for the weaker effect of angiotensin. Continuous infusion increased the output of noradrenaline during several successive stimulation periods.

  4. 4.

    In most cases, the increase in output of noradrenaline induced by angiotensin did not lead to an increase in the response of the pacemaker or of the myocardium to sympathetic stimulation. Only in hearts perfused at constant flow during infusion of 32 ng/min of angiotensin the positive inotropic effect of sympathetic stimulation was significantly augmented.

  5. 5.

    The results indicate that angiotensin may modulate the activity of the autonomic nervous system by influencing peripheral sympathetic nerves.

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Literatur

  • Aiken, J. W., Reit, E.: Stimulation of the cat stellate ganglion by angiotensin. J. Pharmacol. exp. Ther.159, 107–114 (1968).

    Google Scholar 

  • Berry, W. B., Austen, W. G., Clark, W. D.: Studies on the relative cardiac and peripheral actions of angiotensin. Ann. Surg.159, 520–528 (1964).

    Google Scholar 

  • Bianchi, A., de Schaepdryver, A. F., de Vleeschhouwer, G. R., Preziosi, P.: On the pharmacology of synthetic hypertensin. Arch. int. Pharmacodyn.124, 21–44 (1960).

    Google Scholar 

  • Bickerton, R. K., Buckley, J. P.: Evidence for a central mechanism in angiotensin induced hypertension. Proc. Soc. Exp. Biol. (N. Y.)106, 834–836 (1961).

    Google Scholar 

  • Buckley, J. P.: Effects of synthetic angiotensin II on catecholamine levels and biological activity. Acta physiol. scand.65, 273–278 (1966).

    Google Scholar 

  • Cranston, W. I., Lavery, H., Lowe, R. D., Rosendorff, C.: The central pressor effect of angiotensin in the rabbit. J. Physiol. (Lond.)198, 30–31 P (1968).

    Google Scholar 

  • Euler, U. S. v., Floding, I.: A fluorimetric micromethod for differential estimation of adrenaline and noradrenaline. Acta phvsiol. soand.33, Suppl. 118, 45–56 (1955).

    Google Scholar 

  • Farr, W. C., Grupp, G.: Sympathetically mediated effects of angiotensin on the dog heart in situ. J. Pharmacol. exp. Ther.156, 528–537 (1967).

    Google Scholar 

  • Feldberg, W., Lewis, G. P.: The action of peptides on the adrenal medulla. Release of adrenaline by bradykinin and angiotensin. J. Physiol. (Lond.)171, 98–108 (1964).

    Google Scholar 

  • Finkielman, S., Worcel, M., Massani, Z. M., Nahmod, V. E., Paladini, A. C., Agrest, A.: Angiotensin blood levels in hypovolemic shock during osmotic diuresis. Amer. J. Physiol.215, 308–313 (1968).

    Google Scholar 

  • Fowler, N. O., Holmes, J. C.: Coronary and myocardial action of angiotensin. Circulat. Res.14, 191–201 (1964).

    Google Scholar 

  • Haefely, W., Hürlimann, A., Thoenen, H.: Effects of bradykinin and angiotensin on ganglionic transmission. Biochem. Pharmacol.14, 1393 (1965).

    Google Scholar 

  • Heeg, E., Meng, K.: Die Wirkung des Bradykinins, Angiotensins und Vasopressins auf Vorhof, Papillarmuskel und isoliert durchströmte Herzpräparate des Meerschweinchens. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak.250, 35–41 (1965).

    Google Scholar 

  • Hughes, I. E.: Chronotropic and pressor responses to angiotensin in rats anesthetised with urethane. Eur. J. Pharmacol.3, 189–195 (1968).

    Google Scholar 

  • Huković, S., Muscholl, E.: Die Noradrenalin-Abgabe aus dem isolierten Kaninchenherzen bei sympathischer Nervenreizung und ihre pharmakologische Beeinflussung. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak.244, 81–96 (1962).

    Google Scholar 

  • Iversen, L. L.: The uptake and storage of noradrenaline in sympathetic nerves. Cambridge: The University Press 1967.

    Google Scholar 

  • James, T. N.: Absence of direct chronotropic action of angiotensin infused into the sinus node artery. Amer. J. Physiol.209, 571–576 (1965).

    Google Scholar 

  • Koch-Weser, J.: Nature of the inotropic action of angiotensin on ventricular myocardium. Circulat. Res.16, 230–237 (1965).

    Google Scholar 

  • Krasney, J. A., Hogan, P. M., Lowe, R. F., Youmans, W. B.: Peripheral adrenergic basis for cardioaccelerator action of angiotensin. Amer. J. Physiol.211, 1447 to 1450 1966

    Google Scholar 

  • —, Paudler, P. T., Smith, D. C., Davis, L. D., Youmans, W. B.: Mechanisms of cardioaccelerator action of angiotensin. Amer. J. Physiol.209, 539–544 (1965).

    Google Scholar 

  • Kuschinsky, G., Lüllmann, H.: Über die Wirkung von synthetischem Hypertensin auf Kammer- und Vorhofsmuskulatur der Katze. Klin. Wschr.37, 928–931 (1959).

    Google Scholar 

  • Lewis, G. P., Reit, E.: The action of angiotensin and bradykinin on the superior cervical ganglion of the cat. J. Physiol. (Lond.)179, 538–553 (1965).

    Google Scholar 

  • Liebau, H., Distler, A., Wolff, H. P.: Untersuchungen zur indirekten sympathomimetischen Wirkung von Angiotensin an isolierten Blutgefäßen. Klin. Wschr.44, 322–326 (1966).

    Google Scholar 

  • Massani, Z. M., Finkielman, S., Worcel, M., Agrest, A., Paladini, A. C.: Angiotensin blood levels in hypertensive and nonhypertensive diseases. Clin. Sci.30, 473 to 483 (1966).

    Google Scholar 

  • McCubbin, J. W., Page, I. H.: Renal pressor system and neurogenic control of arterial pressure. Circulat. Res.12, 553–559 (1963).

    Google Scholar 

  • Meier, R., Tripod, J., Studer, A.: Comparaison des propriétés vasculaires périphériques de l'hypertensine synthétique et de divers vasoconstricteurs. Arch. int. Pharmacodyn.117, 185–196 (1958).

    Google Scholar 

  • Palaic, D., Khairallah, P. A.: Inhibition of noradrenaline uptake by angiotensin. J. Pharm. Pharmacol.19, 396–397 (1967a).

    Google Scholar 

  • — —: Effect of angiotensin on uptake and release of norepinephrine by brain. Biochem. Pharmacol.16, 2291–2298 (1967b).

    Google Scholar 

  • — —: Inhibition of norepineprine re-uptake by angiotensin in brain. J. Neurochem.15, 1195–1202 (1968).

    Google Scholar 

  • Pals, D. T., Masucci, P. D.: Effect of cocaine, desipramine, and angiotensin on uptake of noradrenaline in tissues of pithed rats. Nature (Lond.)217, 772–773 (1968).

    Google Scholar 

  • Panisset, J. C., Bourdois, P.: Effect of angiotensin on the responses to noradrenaline and sympathetic nerve stimulation, and on3H-noradrenaline uptake in cat mesenteric blood vessels. Can. J. Physiol. Pharmacol.46, 125–131 (1968).

    Google Scholar 

  • Peach, M. J., Ford, G. D.: The actions of angiotensin II on canine myocardial and plasma catecholamines. J. Pharmacol. exp. Ther.162, 92–100 (1968).

    Google Scholar 

  • Ross, G., White, P. N.: Role of catecholamines in cardiovascular responses to angiotensin. Amer. J. Physiol.211, 1419–1423 (1966).

    Google Scholar 

  • Schumann, H. J., Güther, W.: Untersuchungen zum Wirkungsmechanismus von Angiotensin am isolierten Aortenpräparat und am Blutdruck von Ratten und Meerschweinchen. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path.256, 169–182 (1967).

    Google Scholar 

  • Staszewska-Barczak, J., Vane, J. R.: The release of catecholamines from the adrenal medulla by peptides. Brit. J. Pharmacol.30, 655–667 (1967).

    Google Scholar 

  • Thoenen, H., Hürlimann, A., Haefely, W.: The effect of angiotensin on the response to postganglionic sympathetic stimulation of the cat spleen: lack of facilitation of norepinephrine liberation. Med. Pharmacol. exp.13, 379–385 (1965).

    Google Scholar 

  • Walter, P., Bassenge, E.: Effect of angiotensin on vascular smooth muscle. Pflügers Arch.307, 70–82 (1969).

    Google Scholar 

  • Zimmerman, B. G.: Effect of acute sympathectomy on responses to angiotensin and norepinephrine. Circulat. Res.11, 780–787 (1962).

    Google Scholar 

  • —: Evaluation of peripheral and central components of action of angiotensin on the sympathetic nervous system. J. Pharmacol. exp. Ther.158, 1–10 (1967).

    Google Scholar 

  • —, Gisslen, J.: Pattern of renal vasoconstriction and transmitter release during sympathetic stimulation in presence of angiotensin and cocaine. J. Pharmacol. exp. Ther.163, 320–329 (1968).

    Google Scholar 

  • —, Whitmore, L.: Effects of angiotensin and phenoxybenzamine on release of norepinephrine in vessels during sympathetic nerve stimulation. Int. J. Neuropharmacol.6, 27–38 (1967).

    Google Scholar 

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Ausgeführt mit Unterstützung der Deutschen Forschungsgemeinschaft.

Frl. B. Rawe und Herrn J. Urban danken wir für ihre sorgfältige Mitarbeit.

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Starke, K., Werner, U. & Schümann, H.J. Wirkung von Angiotensin auf Funktion und Noradrenalinabgabe isolierter Kaninchenherzen in Ruhe und bei Sympathicusreizung. Naunyn-Schmiedebergs Arch. Pharmak. 265, 170–186 (1969). https://doi.org/10.1007/BF00997149

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