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Interdependence of Antihypertensive, Anticalcinotic, and Antiarteriosclerotic Effects of Calcium Antagonists — Model Experiments on Spontaneously Hypertensive Rats (SHR)

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Cardiovascular Effects of Dihydropyridine-Type Calcium Antagonists and Agonists

Part of the book series: Bayer-Symposium ((BAYER-SYMP,volume 9))

Abstract

In vascular smooth muscle (as in myocardial fibres) a transmembrane supply of Ca++ ions is required for active tension development: Whereas restriction of Ca++ delivery to the contractile system damps mechanical activity, hypercontractile disorders result from a disproportional augmentation of Ca++ entry into the intracellular space. Thus excessive intrusion of Ca++ into the cytoplasm has to be considered the decisive reason for phasic and tonic hyperactivity of the arterial and arteriolar vasculature, culminating in vasospasm. Conversely, Ca++ antagonists which lower transmembrane Ca++ uptake not only in myocardial fibres, but also in smooth muscle (see [6–13, 31]), possess a wide scope of action* against practically all types of vasoconstrictor responses of the coronary, pulmonal, cerebral, renal, or mesenteric arteries.

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References

  1. Belz GG (1970) Die Wirkung des α-Isopropyl-α((N-methyl-N-homoveratril)-γ-aminopropyl)-3,4,5-trimethoxyphenyl-acetonitril auf den Blutdruck des Menschen bei oraler Medikation im akuten Versuch. Arzneim Forsch (Drug Res) 20:799–802.

    CAS  Google Scholar 

  2. Bender F (1970) Die Behandlung der tachykarden Arrhythmien und der arteriellen Hypertonie mit Verapamil. Arzneim Forsch (Drug Res) 20:1310–1316.

    Google Scholar 

  3. Brittinger WD, Schwarzbeck A, Wittenmeier KW, Twittenhoff WD, Stegaru B, Huber W, Ewald RW, v. Henning GE, Fabricius M, Strauch, M (1970) Klinisch-experimentelle Untersuchungen über die blutdrucksenkende Wirkung von Verapamil. Dtsch Med Wschr 95:1871–1877.

    Article  PubMed  CAS  Google Scholar 

  4. Bühler FR (1983) Age and cardiovascular response adaptation: determinants of an antihypertensive treatment concept primarily based on betablockers and calcium entry blockers. Hypertension 5, Suppl 2:94–100.

    Google Scholar 

  5. Fleckenstein A (1964) Die Bedeutung der energiereichen Phosphate fur Kontraktilität und Tonus des Myokards. Verh d Dtschen Gesell f Innere Med 70. Kongreß, S 81–99.

    CAS  Google Scholar 

  6. Fleckenstein A (1970/1971) 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. In: Harris P, Opie L (eds) Calcium and the heart. Proceed. of the Meeting of the Europ Section of the Internat Study Group for Research in Cardiac Metabolism, London, Sept. 1970. Academic Press, London New York, pp 135–188.

    Google Scholar 

  7. Fleckenstein A (1977) Specific pharmacology of calcium in myocardium, cardiac pacemakers, and vascular smooth muscle. Ann Rev Pharmacol Toxicol 17:149–166.

    Article  CAS  Google Scholar 

  8. Fleckenstein A (1981) Fundamental actions of calcium antagonists on myocardial and cardiac pacemaker cell membranes. In: Weiss GB (ed) New perspectives on calcium antagonists. Clin Physiol Series, American Physiological Society, pp 59-81.

    Google Scholar 

  9. Fleckenstein A (1982) Basic membrane actions of calcium antagonists with special reference to verapamil. In: Godfraind T, Albertini A, Paoletti R (eds) Calcium modulators. Proceed. of an Internat. Symp. on Calcium Modulators, Venice, June 1982. Elsevier Biomedical Press, Amsterdam New York Oxford, pp 297–310.

    Google Scholar 

  10. Fleckenstein A (1983) History of calcium antagonists. In: Schwartz A, Taira N (eds) Calcium channel-blocking drugs: A novel intervention for the treatment of cardiac disease. Monograph Nr. 95 of the American Heart Association, Circ Research, Part II, Vol. 52, No. 2, pp 3–16.

    CAS  Google Scholar 

  11. Fleckenstein A (1983) Calcium antagonism in heart and smooth muscle — Experimental facts and therapeutic prospects. John Wiley, New York Chichester Brisbane Toronto Singapore.

    Google Scholar 

  12. Fleckenstein A (1984) Calcium antagonism: History and prospects for a multifaceted pharmacodynamic principle. In: Opie LH (ed) Calcium antagonists and cardiovascular disease. Raven Press, New York, pp 9–28.

    Google Scholar 

  13. Fleckenstein A, Döring HJ, Janke J, Byon YK (1975) Basic actions of ions and drugs on myocardial high-energy phosphate metabolism and contractility. In: Handbook of experimental pharmacology, Vol. XVI/3. Springer Berlin Heidelberg New York, pp 345–405.

    Google Scholar 

  14. Fleckenstein A, Fleckenstein-Grün G (1980) Cardiovascular protection by Ca antagonists. Europ Heart J 1:15–21.

    CAS  Google Scholar 

  15. Fleckenstein A, Frey M, Fleckenstein-Grün G (1983) Protection by calcium antagonists against experimental arterial calcinosis. In: Pyörälä K, Rapaport E, König K, Schettler G, Diehm C (eds) Secondary prevention of coronary heart disease. Workshop of the Internat Soc and Federation of Cardiology, Titisee, Oct. 1983. Thieme, Stuttgart New York, pp 109–122.

    Google Scholar 

  16. Fleckenstein A, Frey M, Leder O (1982/83) Prevention by calcium antagonists of arterial calcinosis. In: Fleckenstein A, Hashimoto K, Herrmann M, Schwartz A, Seipel L (eds) Drug development and evaluation — New calcium antagonists — Recent developments and prospects, Diltiazem Workshop, Freiburg/Germany, May 1982. Fischer, Stuttgart New York, pp 15–31.

    Google Scholar 

  17. Fleckenstein A, Frey M, v. Witzleben H (1982/83) Vascular calcium overload — a pathogenetic factor in arteriosclerosis and its neutralization by calcium antagonists. In: Kaltenbach M, Neufeld, HN (eds) New therapy of ischemic heart disease and hypertension. Proceed. of the 5th Internat Adalat Symp, Berlin, May 1982. Excerpta Medica, Amsterdam Oxford Princeton, pp 36–52.

    Google Scholar 

  18. Fleckenstein A, Grün G, Byon YK, Döring HJ, Tritthart H (1975) The basic Ca antagonistic actions of nifedipine on cardiac energy metabolism and vascular smooth muscle tone. In: Hashimoto K, Kimura E, Kobayashi T (eds) New therapy of ischemic heart disease. 1st Internat Adalat Symposium, Tokyo, 1975. University of Tokyo Press, pp 31-44.

    Google Scholar 

  19. Fleckenstein A, Nakayama K, Fleckenstein-Grün G, Byon YK (1975) Interactions of vasoactive ions and drugs with Ca-dependent excitation contraction coupling of vascular smooth muscle. In: Carafoli E, Clementi F, Drabikowski W, Margreth A (eds) Calcium transport in contraction and secretion. Proceed. of an Internat Symp in Bressanone/Italy, Mai 1975. North Holland, Amsterdam Oxford; American Elsevier, New York, pp 555–566.

    Google Scholar 

  20. Fleckenstein A, Tritthart H, Döring HJ, Byon YK (1972) Bay a 1040 — ein hochaktiver Ca++-antagonistischer Inhibitor der elektro-mechanischen Koppelungsprozesse im Warmblüter-Myokard. Arzneim Forsch (Drug Res) 22:22–33.

    CAS  Google Scholar 

  21. Fleckenstein-Grün G, Fleckenstein A (1980/81) Calcium antagonism, a basic principle in vasodilation. In: Zanchetti A, Krikler DM (eds) Calcium antagonism in cardiovascular therapy: Experience with verapamil. Internat Symp, Florence/Italy, Oct. 1980. Excerpta Medica, Amsterdam Oxford Princeton, pp 30–48.

    Google Scholar 

  22. Frey M, Keidel J, Fleckenstein A (1978/80) Verhütung experimenteller Gefäßverkalkungen (Mönckebergs Typ der Arteriosklerose) durch Calcium-Antagonisten bei Ratten. In: Flekkenstein A, Roskamm H (eds) Calcium-Antagonismus Proceed Internat Symp, Frankfurt, 1978. Springer, Berlin Heidelberg New York, pp 258–264.

    Google Scholar 

  23. Garthoff B, Kazda S (1981) Calcium antagonist nifedipine normalizes high blood pressure and prevents mortality in salt-loaded DS substrain of Dahl rats. Eur J Pharmacol 74:111–112.

    Article  PubMed  CAS  Google Scholar 

  24. Grün G, Bayer M, Fleckenstein A (1972) Der Einfluß des pH äuf den Ca++-abhängigen Tonus der Coronar-Gefäßmuskulatur. Naunyn-Schmiedebergs Arch Pharmakol, Suppl to vol 274, R 43.

    Google Scholar 

  25. Grün G, Fleckenstein A (1972) Die elektro-mechanische Entkoppelung der glatten Gefäß-muskulatur als Grundprinzip der Coronardilatation durch 4-(2′-Nitrophenyl)-2,6-dimethyl-1,4-dihydropyridin-3,5-dicarbonsäure-dimethylester (Bay a 1040, Nifedipin). Arzneim Forsch (Drug Res) 22:334–344.

    Google Scholar 

  26. Grün G, Weder U, Fleckenstein A (1972) The mutual antagonism between H and Ca ions in the control of vascular tone and autoregulation. Pflügers Arch ges Physiol Suppl to Vol. 335, R10.

    Article  Google Scholar 

  27. Heidland A, Klütsch K, Öbek A (1962) Myogenbedingte Vasodilatation bei Nierenischämie. Münch Med Wschr 104:1636–1637.

    PubMed  CAS  Google Scholar 

  28. Hiwatari M, Taira N (1979) Antihypertensive effect of niludipine (Bay a 7168) on conscious renal-hypertensive dogs. Arzneim Forsch (Drug Res) 29:1373–1376.

    CAS  Google Scholar 

  29. Janke J, Hein B, Pachinger O, Leder O, Fleckenstein A (1972) Hemmung arteriosklerotischer Gefäßprozesse durch prophylaktische Behandlung mit MgCl2, KCl und organischen Ca++-Antagonisten (quantitative Studien mit Ca45 bei Ratten). In: Betz E (ed) Vascular smooth muscle. Proc. Satellit Symp XXV. Internat Congr Physiol Sciences, Tubingen, Mi 1971. Springer, Berlin Heidelberg New York, pp 71–72.

    Google Scholar 

  30. Kiyomoto A (1978/79) Antihypertensive effects of diltiazem in rats. In: Bing RJ (ed) New drug therapy with a calcium antagonist, Diltiazem. Hakone Symp, 1978. Excerpta Medica, Amsterdam Princeton, pp 112–125.

    Google Scholar 

  31. Kohlhardt M, Bauer B, Krause H, Fleckenstein A (1972) Differentiation of the transmembrane Na and Ca channels in mammalian cardiac fibres by the use of specific inhibitors. Pflügers Arch ges Physiol 335:309–322.

    Article  CAS  Google Scholar 

  32. Laragh JH (1984) Proceed. of a Symp. on “Calcium Metabolism and Calcium Channel Blockers for Understanding and Treating Hypertension”. Amer J Med 77(Suppl 6 B) 1–23.

    PubMed  CAS  Google Scholar 

  33. Nakajima H, Hoshiyama M, Yamashita K, Kiyomoto A (1975) Effect of diltiazem on electrical and mechanical activity of isolated cardiac ventricular muscle of guinea pig. Jpn J Pharmacol 25:383–392.

    Article  PubMed  CAS  Google Scholar 

  34. Takahashi S (1972) On the fundus of spontaneously hypertensive rats. In: Okamoto K (ed) Spontaneous hypertension. Its pathogenesis and complications, Igaku Shoin, Tokyo; Springer, Berlin Heidelberg New York, pp 160–165.

    Google Scholar 

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Authors
  1. A. Fleckenstein
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  2. M. Frey
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  3. J. Zorn
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  4. G. Fleckenstein-Grün
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Editor information

Editors and Affiliations

  1. Physiologisches Institut, Universität Freiburg, Hermann-Herder-Straße 7, D-7800, Freiburg i. Br., Germany

    Albrecht Fleckenstein

  2. Department of Pharmacology, University of Miami School of Medicine, P.O. Box 016189, Miami, FL, 33101, USA

    Cornelius Van Breemen D.V.M., Ph.D.

  3. Abteilung Herz-Kreislauf-Pharmakologie II, Bayer AG, Institut für Pharmakologie, Postfach 10 1709, D-5600, Wuppertal 1, Germany

    Rainer Gross

  4. Bayer AG, Institut für Pharmakologie, Postfach 10 1709, D-5600, Wuppertal 1, Germany

    Friedrich Hoffmeister

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© 1985 Springer-Verlag Berlin Heidelberg

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Fleckenstein, A., Frey, M., Zorn, J., Fleckenstein-Grün, G. (1985). Interdependence of Antihypertensive, Anticalcinotic, and Antiarteriosclerotic Effects of Calcium Antagonists — Model Experiments on Spontaneously Hypertensive Rats (SHR). In: Fleckenstein, A., Van Breemen, C., Gross, R., Hoffmeister, F. (eds) Cardiovascular Effects of Dihydropyridine-Type Calcium Antagonists and Agonists. Bayer-Symposium, vol 9. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-70499-4_32

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  • DOI: https://doi.org/10.1007/978-3-642-70499-4_32

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-70501-4

  • Online ISBN: 978-3-642-70499-4

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