Summary
Electrophysiological and mechanical effects of phenylephrine were observed in the rabbit papillary muscle which was depolarized and rendered inexcitable by an elevation of potassium concentration to 27 mM in the presence of a β-adrenoceptor blocking drug, bufetolol (10−6 M).
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1.
Phenylephrine (10−6 to 10−4 M) restored the action potential and tension development. The amplitude, duration and maximum rate of rise of the action potential, and developed tension were augmented by an increase in the concentration of phenylephrine.
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2.
The amplitude of the action potential restored by phenylephrine was very sensitive to the Ca2+ concentration and increased by 29.2 mV/10-fold increase crease in external Ca2+ concentration. Nifedipine (10−6 M), a Ca2+ antagonist, completely suppressed the electrical and mechanical responses restored by phenylephrine (10−5 M), but tetrodotoxin (10−5 M) had little effect on these responses.
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3.
Phentolamine (10−6 M) suppressed both the action potential and developed tension restored by phenylephrine (10−5 M), but the elevation of the concentration of bufetolol from 10−6 M to 3×10−6 M was ineffective against these responses.
In conclusion, the restoration by phenylephrine of Ca2+-dependent action potential may be ascribed to an enhancement of the inward Ca2+ current, mediated by α-adrenoceptors and this mechanism may play an important role in the α-adrenoceptor-mediated positive inotropic effect.
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References
Beeler, G. W., Jr., Reuter, H.: Voltage clamp experiments on ventricular myocardial fibres. J. Physiol. (Lond.) 207, 165–190 (1970)
Brodde, O. E., Motomura, S., Schümann, H. J.: Does the positive inotropic effect of phenylephrine (PE) evoked by α-adrenoceptor stimulation influence the cyclic 3′,5′-AMP and/or-GMP level in the isolated rabbit ventricular strips? Naunyn-Schmiedeberg's Arch. Pharmacol. 294, R18 (1976)
Cranefield, P. F., Hoffman, B. F., Wit, A. L.: Block of conduction in partially depolarized cardiac Purkinje fibres induced by an α-adrenergic agent. Nature (Lond.) 234, 159–160 (1971)
Endoh, M., Brodde, O. E., Schümann, H. J.: Relationship between the level of cAMP and the contractile force under stimulation of α- and β-adrenoceptors by phenylephrine in the isolated rabbit papillary muscle. Naunyn-Schmiedeberg's Arch. Pharmacol. 295, 109–115 (1976)
Endoh, M., Wagner, J., Schümann, H. J.: Influence of temperature on the positive inotropic effects mediated by α- and β-adrenoceptors in the isolated rabbit papillary muscle. Naunyn-Schmiedeberg's Arch. Pharmacol. 287, 61–72 (1975)
Govier, W. C.: Myocardial alpha adrenergic receptors and their role in the production of a positive inotropic effect by sympathomimetic agents. J. Pharmacol. Exp. Ther. 159, 82–97 (1968)
Harrington, L., Johnson, E. A.: Voltage clamp of cardiac muscle in a double sucrose gap. A feasibility study. Biophys. J. 13, 626–647 (1973)
Hauswirth, O., Wehner, H. D., Ziskoven, R.: α-Adrenergic receptors and pacemaker current in cardiac Purkinje fibres. Nature (Lond.) 263, 155–156 (1976)
Inui, J., Imamura, H.: Restoration by histamine of the calcium-dependent electrical and mechanical response in the guinea-pig papillary muscle partially depolarized by potassium. Naunyn-Schmiedeberg's Arch. Pharmacol. 294, 261–269 (1976)
Inui, J., Imamura, H.: β-Adrenoceptor blocking and electrophysiological effects of bufetolol in the guinea pig atria. Eur. J. Pharmacol. 41, 251–260 (1977)
Kohlhardt, M., Fleckenstein, A.: Inhibition of the slow inward current by nifedipine in mammalian ventricular myocardium. Naunyn-Schmiedeberg's Arch. Pharmacol. 298, 267–272 (1977)
Kukovetz, W. R., Pöch, G., Wurm, A.: Quantitative relations between cyclic AMP and contraction as affected by stimulators of adenylate cyclase and inhibitors of phosphodiesterase. Adv. Cyclic Nucleotide Res. 5, 395–414 (1975)
Ledda, F., Marchetti, P., Mugelli, A.: Studies on the positive inotropic effect of phenylephrine: a comparison with isoprenaline. Br. J. Pharmacol. 54, 83–90 (1975)
Meinertz, T., Nawrath, H., Scholz, H.: Stimulatory effects of DB-c-AMP and adrenaline on myocardial contraction and 45Ca exchange. Experiments at reduced calcium concentration and low frequencies of stimulation. Naunyn-Schmiedeberg's Arch. Pharmacol. 279, 327–338 (1973)
Mugelli, A., Ledda, F., Mantelli, L.: Frequency dependence of the α-adrenoceptor-mediated positive inotropic effect in guinea pig heart. Eur. J. Pharmacol. 36, 215–220 (1976)
Pappano, A. J.: Calcium-dependent action potentials produced by catecholamines in guinea pig atrial muscle fibers depolarized by potassium. Circ. Res. 27, 379–390 (1970)
Reuter, H.: Divalent cations as charge carriers in excitable membranes. Prog. Biophys. Mol. Biol. 26, 1–43 (1973)
Reuter, H.: Localization of beta adrenergic receptors, and effects of noradrenaline and cyclic nucleotides on action potentials, ionic currents and tension in mammalian cardiac muscle. J. Physiol. (Lond.) 242, 429–451 (1974)
Schneider, J. A., Sperelakis, N.: The demonstration of energy dependence of the isoproterenol-induced transcellular Ca2+ current in isolated perfused guinea pig hearts—An explanation for mechanical failure of ischemic myocardium. J. Surg. Res. 16, 389–403 (1974)
Schümann, H. J., Endoh, M., Wagner, J.: Positive inotropic effects of phenylephrine in the isolated rabbit papillary muscle mediated both by α- and β-adrenoceptors. Naunyn-Schmiedeberg's Arch. Pharmacol. 284, 133–148 (1974)
Shigenobu, K., Schneider, J. A., Sperelakis, N.: Verapamil blockade of slow Na+ and Ca2+ responses in myocardial cells. J. Pharmacol. Exp. Ther. 190, 280–288 (1974)
Tsien, R. W.: Effects of epinephrine on the pacemaker potassium current of cardiac Purkinje fibers. J. Gen. Physiol. 64, 293–319 (1974)
Verma, S. C., McNeill, J. H.: Biochemical and mechanical effects of phenylephrine on the heart. Eur. J. Pharmacol. 36, 447–450 (1976)
Wagner, J., Endoh, M., Reinhardt, D.: Stimulation by phenylephrine of adrenergic alpha- and beta-receptors in the isolated perfused rabbit heart. Naunyn-Schmiedeberg's Arch. Pharmacol. 282, 307–310 (1974)
Wenzel, D. G., Su, J. L.: Interactions between sympathomimetic amines and blocking agents on the rat ventricle strip. Arch. Int. Pharmacodyn. 160, 379–389 (1966)
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Miura, Y., Inui, J. & Imamura, H. Alpha-adrenoceptor-mediated restoration of calcium-dependent potential in the partially depolarized rabbit papillary muscle. Naunyn-Schmiedeberg's Arch. Pharmacol. 301, 201–205 (1978). https://doi.org/10.1007/BF00507038
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DOI: https://doi.org/10.1007/BF00507038