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. 1975 May;54(1):83–90. doi: 10.1111/j.1476-5381.1975.tb07413.x

Studies on the positive inotropic effect of phenylephrine: a comparison with isoprenaline.

F Ledda, P Marchetti, A Mugelli
PMCID: PMC1666381  PMID: 1139077

Abstract

1. The effects of phenylephrine and isoprenaline on the isometric contraction of guinea-pig ventricle were compared over the whole range of their respective dose-response curves. 2. In preparations driven at 2.5 Hz the increase in contractile force induced by either isoprenaline of phenylephrine was linearly correlated to an increase in maximum velocity of force development. The relaxation time was shortened by isoprenaline but not by phenylephrine. 3. The negative inotropic effect induced by delta [N-(3,4-dimethoxyphenethyl)-N-methyl-amino]-alpha-(3,4,5-trimethoxyphenyl)alpha-isopropylvaleronitrile hydrochloride (D(600)) was reversed by isoprenaline, but little influenced by phenylephrine. 4. The study of the interval-force relationship shows that the increase in contractile force induced by phenylephrine (3 X 10(-5) M) was relatively greater at low frequencies of stimulation, and that the maximum effect was reached at the frequency of 1 Hz. 5. The positive inotropic effect of phenylephrine (10-4 M) was significantly higher at a frequency of 1 Hz than at 2.5 Hz; the effect of isoprenaline (3 x 10-8 M) was not significantly different at the two driving frequencies. 6. In preparations driven at 1 Hz the inotropic effect of the lower concentrations of phenylephrine was due to an increase in the time to peak tension without any change of the maximum velocity of force development; however an increase of this parameter became evident only after higher concentrations of the amine (10-5 M or more), associated with a progressive shortening of the time to peak. 7. A correlation between mechanical and electrophysiological effects of phenylephrine is attempted; the suggestion is advanced that the prolongation of the action potential and of the active state duration may be an important factor in the inotropic effect of phenylephrine.

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Selected References

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  1. Benfey B. G., Carolin T. Effect of phenylephrine on cardiac contractility and adenyl cyclase activity. Can J Physiol Pharmacol. 1971 Jun;49(6):508–512. doi: 10.1139/y71-065. [DOI] [PubMed] [Google Scholar]
  2. Benfey B. G. Characterization of -adrenoceptors in the myocardium. Br J Pharmacol. 1973 May;48(1):132–138. doi: 10.1111/j.1476-5381.1973.tb08230.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Benfey B. G. Lack of relationship between myocardial cyclic AMP concentrations and inotropic effects of sympathomimetic amines. Br J Pharmacol. 1971 Dec;43(4):757–763. doi: 10.1111/j.1476-5381.1971.tb07211.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Benfey B. G., Varma D. R. Interactions of sympathomimetic drugs, propranolol and phentolamine, on atrial refractory period and contractility. Br J Pharmacol Chemother. 1967 Aug;30(3):603–611. doi: 10.1111/j.1476-5381.1967.tb02166.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Giotti A., Ledda F., Mannaioni P. F. Effects of noradrenaline and isoprenaline, in combination with - and -receptor blocking substances, on the action potential of cardiac Purkinje fibres. J Physiol. 1973 Feb;229(1):99–113. doi: 10.1113/jphysiol.1973.sp010129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Govier W. C. A positive inotropic effect of phenylephrine mediated through alpha adrenergic receptors. Life Sci. 1967 Jul 1;6(13):1361–1365. doi: 10.1016/0024-3205(67)90182-8. [DOI] [PubMed] [Google Scholar]
  7. 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. 1968 Jan;159(1):82–90. [PubMed] [Google Scholar]
  8. Hamakawa H., Shimizu T., Toda N. Interactions of phenylephrine and theophylline in contractility and excitability of isolated rabbit left atria. Jpn J Pharmacol. 1973 Jun;23(3):373–379. doi: 10.1254/jjp.23.373. [DOI] [PubMed] [Google Scholar]
  9. Kohlhardt M., Bauer B., Krause H., Fleckenstein A. New selective inhibitors of the transmembrane Ca conductivity in mammalian myocardial fibres. Studies with the voltage clamp technique. Experientia. 1972 Mar 15;28(3):288–289. doi: 10.1007/BF01928693. [DOI] [PubMed] [Google Scholar]
  10. Kukovetz W. R., Pöch G. The positive inotropic effect of cyclic AMP. Adv Cyclic Nucleotide Res. 1972;1:261–290. [PubMed] [Google Scholar]
  11. Ledda F., Marchetti P. Electrophysiological effects of phenylephrine on Purkinje fibres of sheep heart. Arch Int Pharmacodyn Ther. 1972 Apr;196(Suppl):117–117. [PubMed] [Google Scholar]
  12. Morad M., Trautwein W. The effect of the duration of the action potential on contraction in the mammalian heart muscle. Pflugers Arch Gesamte Physiol Menschen Tiere. 1968;299(1):66–82. doi: 10.1007/BF00362542. [DOI] [PubMed] [Google Scholar]
  13. Pappano A. J. Propranolol-insensitive effects of epinephrine on action potential repolarization in electrically driven atria of the guinea pig. J Pharmacol Exp Ther. 1971 Apr;177(1):85–95. [PubMed] [Google Scholar]
  14. Parr J. J., Urquilla P. R. Analysis of the adrenergic receptors of pacemaker and myocardial cells. Eur J Pharmacol. 1972 Jan;17(1):1–7. doi: 10.1016/0014-2999(72)90261-0. [DOI] [PubMed] [Google Scholar]
  15. VAN ROSSUM J. M. Cumulative dose-response curves. II. Technique for the making of dose-response curves in isolated organs and the evaluation of drug parameters. Arch Int Pharmacodyn Ther. 1963;143:299–330. [PubMed] [Google Scholar]
  16. Vassort G., Rougier O. Membrane potential and slow inward current dependence of frog cardiac mechanical activity. Pflugers Arch. 1972;331(3):191–203. doi: 10.1007/BF00589126. [DOI] [PubMed] [Google Scholar]
  17. Wenzel D. G., Su J. L. Interactions between sympathomimetic amines and blocking agents on the rat ventricle strip. Arch Int Pharmacodyn Ther. 1966 Apr;160(2):379–389. [PubMed] [Google Scholar]

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