Cardiology pp 45-51 | Cite as

Calcium and Cardiovascular Disease

  • L. H. Opie
Chapter

Abstract

When the calcium-antagonist agents were initially used by Fleckenstein’s group, it was found that beta-adrenoceptor agonists opposed the specific action of high dose verapamil (10-5M) in inhibiting myocardial contractility (Figure 3 and 7 in Fleckenstein, 1971). The restorative effect of isoproterenol was very similar to that of an increased extracellular calcium (Figure 6 in Fleckenstein, 1971). Thus early thinking saw calcium-antagonists and beta-antagonists as having opposite effects on trans-sarcolemmal calcium flux. Some even argued that the calcium-antagonists had beta-blocking qualities, an argument that was laid to rest when it was found that verapamil was unable to inhibit an isoproterenol-induced tachycardia or inotropic response (Nayler et al, 1968). The explanation was that verapamil could not prevent catecholamine-induced increases in the tissue level of cyclic AMP nor the beta-mediated activation of adenyl cyclase; rather, verapamil blocked the trans-sarcolemmal calcium influx provoked in K+ depolarized hearts by either catecholamines or by an increased external calcium (Watanabe et al, 1974).

Keywords

Calcium Channel Ventricular Fibrillation Coronary Artery Ligation Coronary Ligation Ventricular Fibrillation Threshold 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References

  1. Bassingthwaighte, J. B., Fry, C. H., McGuigan, J. A. S., 1976. Relationship between internal calcium and outward current in mammalian ventricular muscle: a mechanism for the control of the action potential duration? J. Physiol. 262: 15–37.PubMedGoogle Scholar
  2. Bayer, R., Kalusche, D., Kaufmann, R., Mannhold, R., 1975. Inotropic and electrophysiological actions of verapamil and D600 in mammalian myocardium. 111. Effects of the optical isomers on transmembrane action potentials. Naunyn-Schmied. Arch. Pharm. 290: 81–97.CrossRefGoogle Scholar
  3. Bolton, T. B., 1979. Mechanisms of action of transmitters and other substances on smooth muscle. Physiol. Rev. 59: 606–718.PubMedGoogle Scholar
  4. Bondi, A. Y., 1978. Effects of verapamil on excitation-contraction coupling in frog sartorius muscle. J. Pharmacol. Expt. Therap. 205: 49–57.Google Scholar
  5. Boström, S.L., Ljung, B., Mardh, S., Forsen, S., Thulin, E., 1981. Interaction of the antihypertensive drug felodipine with calmodulin. Nature 292: 777–778.PubMedCrossRefGoogle Scholar
  6. Fleckenstein, A., 1971. Specific inhibitors and promoters of calcium action in the excitation-contraction coupling of heart muscle and their role in the prevention or production of myocardial lesions. Harris, P., Opie, L.H. eds. In “Calcium and the Heart” London: Academic Press; 135–188Google Scholar
  7. Hamm, C. W., Thandroyen, F. T., Opie, L. H., 1982. Protective effects on isolated hearts with developing infarction: slow channel blockade by diltiazem versus beta-adrenoceptor antagonism by metoprolol. Am. J. Cardiol, in pressGoogle Scholar
  8. Hariman, R. J., Mangiardi, L. M., McAllister, R. G., Surawicz, B., Shabetai, R., Kishida, H., 1979. Reversal of the cardiovascular effects of verapamil by calcium and sodium: differences between electrophysiologic and hemodynamic responses. Circulation 59: 797–804.PubMedCrossRefGoogle Scholar
  9. Hidaka, H., Yamaki, T., Naka, M., Tanaka, T., Hayashi, H., Kobayashi, R., 1979. Calcium-regulated modulator protein interacting agents inhibit smooth muscle calcium-stimulated protein kinase and ATPase. Mol. Pharmacol. 17: 66–72.Google Scholar
  10. Kolhardt, M., Mnich, Z., 1978. Studies on the inhibitory effect of verapamil on the slow inward current in mammalian ventricular myocardium. J. Molec. Cell Cardiol. 10: 1037–1052.CrossRefGoogle Scholar
  11. Langer, G. A., Serena, S. D., Nubb, L. M., 1975. Localization of contractile-dependent Ca: comparison of Mn and verapamil in cardiac and skeletal muscle. Am. J. Physiol. 229: 1003–1007.PubMedGoogle Scholar
  12. Lubbe, W. F., Muller, C. A., Worthington, M. G., McFadyen, L., Opie, L. H., 1981. Influence of propranolol isomers and atenolol on myocardial cyclic AMP, high energy phosphates and vulnerability to fibrillation after coronary artery ligation in the isolated rat heart. Cardiovasc. Res. 15: 690–699;PubMedCrossRefGoogle Scholar
  13. Lubbe, W. F., Podzuweit, T., Daries, P. S., Opie, L. H., 1978. The role of cyclic adenosine monophosphate in adrenergic effects on vulnerability to fibrillation in the isolated perfused rat heart. J. Clin. Invest. 61: 1260–1269.PubMedCrossRefGoogle Scholar
  14. Lullman, H., Timmermans, P. B., Ziegler, A., 1979, Accumulation of drugs by resting or beating cardiac tissue. Europ. J. Pharmacol. 60: 277–285.CrossRefGoogle Scholar
  15. Nayler, W. G., Mclnnes, I., Swann, J. B., Price, J. M., Carson, V., Race, C., Lowe, T. E., 1968. Some effects of iproveratril (Isoptin) on the cardiovascular system, J. Pharmacol. Expt. Therap. 161: 247–261.Google Scholar
  16. Opie, L. H., Muller, C., Nathan, D., Daries, P., Lubbe, W. F., 1980. Evidence for role of cyclic AMP as second messenger of arrhyth-mogenic effects of beta-stimulation. Adv. Cycl. Nucl. Res. 12: 63–69.Google Scholar
  17. Opie, L. H., Thandroyen, F. T., Hamm, C. W., 1982. Beta-blockade: metabolic and antiarrhythmic effects in myocardial infarction. Calcium as third messenger. In: Advances in beta-blocker therapy 11. Excerpta Medica; Amsterdam, pp. 40–64.Google Scholar
  18. Opie, L. H., Thandroven, F. T., Muller, C., Bricknell, O. L., 1979. Adrenaline-induced “oxygen-wastage” and enzyme release from working rat heart. Effects of calcium antagonism, ß-blockade, nicotinic acid and coronary artery ligation. J. Molec. Cell. Cardiol. 11: 1073–1094.CrossRefGoogle Scholar
  19. Payet, M. D., Schanne, O. F., Ruiz-Ceretti, E., Demers, J. M., 1980. Inhibitory action of blockers of the slow inward current in rat myocardium, a study in steady state and rate of action. J. Molec. Cell Cardiol. 12: 187–200.CrossRefGoogle Scholar
  20. Reuter, H., 1974. 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. 242: 429–451.PubMedGoogle Scholar
  21. Reuter, H., Scholtz, 1977. The regulation of the calcium conductance of cardiac muscle by adrenaline. J. Physiol. 264: 49–62.PubMedGoogle Scholar
  22. Schneider, J. A., Sperelakis, N., 1975. Slow Ca2+ and Na+ responses induced by isoproterenol and methylxanthines in isolated perfused guinea pig hearts exposed to elevated K+. J. Molec. Cell Cardiol. 7: 249–273.CrossRefGoogle Scholar
  23. Thandroyen, F. T., 1982. Protective action of calcium channel antagonist agents against ventricular fibrillation in the isolated perfused rat heart. J. Molec. Cell. Cardiol. 14: 21–32.CrossRefGoogle Scholar
  24. Towart, R., 1981. The selective inhibition of serotonin-induced contractions of rabbit cerebral vascular smooth muscle by calcium-antagonistic dihydropyridines. An investigation of the mechanism of action of nimodipine. Circ. Res. 48: 650–657.PubMedCrossRefGoogle Scholar
  25. Van Breemen, C., Mangel, A., Fahim, M., Meisheri, K., 1982. Selectivity of calcium antagonist action in vascular smooth muscle. Am. J. Cardiol. 49: 507–510.PubMedCrossRefGoogle Scholar
  26. Van Meel, J. C. A., de Jonge, A., Kalkman, H. D., Wilffert, B., Timmermans, B. M. W. M., van Zwieten, P. A., 1981. Vascular smooth muscle contraction initiated by postsynaptic α2-adrenoceptor activation is induced by an influx of extracellular calcium. Europ. J. Pharmacol. 69: 205–208.CrossRefGoogle Scholar
  27. Watanabe, A. M., Besch, H. R. Jr., 1974. Subcellular myocardial effects of verapamil and D600: comparison with propranolol. J. Pharmacol. Expt. Therap. 191: 241–251.Google Scholar
  28. Weld, F. M., Coromilas, J., Rottman, J. N., Bigger, J. T. Jr., 1982. Mechanisms of quinidine-induced depression of maximum upstroke velocity in ovine cardiac Purkinje fibers. Circ. Res. 50: 369–376.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • L. H. Opie
    • 1
  1. 1.MRC Ischaemic Heart Research Unit Department of MedicineGroote Schuur Hospital and University of Cape TownSouth Africa

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