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Drugs

, Volume 48, Supplement 1, pp 32–39 | Cite as

Future Prospects for Calcium Antagonists

  • S. Kazda
Short Communication

Summary

In hypertensive disease, calcium antagonists (CA) affect the limiting step of increased vascular resistance.

In the future, it is likely that the use of calcium antagonists will be extended to the early stage of hypertension, which is characterised predominantly by preglomerular vasoconstriction and only discrete impairment of renal function. In the advanced stages of hypertension they will be used to prevent vascular remodelling and to limit renal and cardiac tissue damage.

By preventing excessive calcium overload, calcium antagonists preserve tissue integrity and reverse the progression of specific vascular pathologies such as arteriosclerosis and microangiopathy through mechanisms independent of their blood pressure-lowering effect.

The protective effect demonstrated by nifedipine against toxic and radiation-induced changes in nonvascular tissue in animal models merits specific attention.

Keywords

Adis International Limited Nifedipine Calcium Antagonist Nisoldipine Calcium Entry Blocker 
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. 1.
    Yanagisawa M, Kurihara H, Kimura S, et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 1988; 332: 411–5.PubMedCrossRefGoogle Scholar
  2. 2.
    Lewanczuk RZ, Wang J, Zhang ZR, et al. Effects of spontaneously hypertensive rat plasma on blood pressure and tail artery calcium uptake in normotensive rats. Am J Hypertens 1989; 2: 26–31.PubMedGoogle Scholar
  3. 3.
    Kazda S, Scriabine A. Pharmacology of nifedipine. In: Krebs R, editor. Treatment of cardiovascular disease by Adalat® (nifedipine), Stuttgart: Schattauer Verlag 1986: 43–92Google Scholar
  4. 4.
    Kazda S, Garthoff B, Meyer H, et al. Pharmacology of a new calcium antagonistic compound, isobutyl-methyl- 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinecaboxy-late (Nisoldipine, BAY k 5552). Arzneimittelforschung 1980; 30: 2144–62.PubMedGoogle Scholar
  5. 5.
    Godfraind T, Morel N, Wibo M. Mechanisms of the vascular selectivity of nisoldipine. In: Lichtlen & Hugenholtz, editors. Nisoldipine. Stuttgart: Schattauer-Verlag 1988: 25–37.Google Scholar
  6. 6.
    Richter JA, Barankay A, Späth P, et al. Prophylactic use of nifedipine and its effects on hemodynamic parameters, plasma and tissue concentrations and endogenous catecholamines during CABG operation. In: Hempelmann et al., editors. Adalat pro infusione. Stuttgart: Schattauer Verlag 1993: 68–76Google Scholar
  7. 7.
    Guyton AC, Coleman TG, Cowley AW, et al. Arterial pressure regulation: overriding dominance of the kidneys in long-term regulation and hypertension. Am J Med 1972; 52: 584–94.PubMedCrossRefGoogle Scholar
  8. 8.
    Ruilope LM, Alcazar JM. Renal effects of calcium entry blockers. Cardiovasc Drugs Ther 1990; 4: 979–82.PubMedCrossRefGoogle Scholar
  9. 9.
    Klütsch K, Schmidt P, Grosswendt J. Der Einfluβ von BAY a 1040 auf die Nierenfunktion des Hypertonikers. Arzneimittelforschung 1972; 22: 377–80.PubMedGoogle Scholar
  10. 10.
    Puschett JB, Dalomino C, Wallia R, et al. The acute effects of nitrendipine on the human kidney. J Cardiovasc Pharmacol 1987; 9 Suppl. 4: S169–73.Google Scholar
  11. 11.
    Johns EJ, Manitius J. The renal actions of nitrendipine and its influence on the renal regulation of calcium and sodium reabsorption in the rat. J Cardiovasc Pharmacol 1987; 9 Suppl. 1: S49–56.PubMedGoogle Scholar
  12. 12.
    Leonetti G, Zanchetti A. Renal effects of calcium antagonists in hypertensive patients. J Hypertens 1985; 3 Suppl. 3: 535–9.Google Scholar
  13. 13.
    Lederballe-Pedersen O, Krusell LR, Christensen CK, et al. Effect of calcium antagonists in essential hypertension with special reference to renal function. In: Aoki K, editor. Essential hypertension, pp. Berlin: Springer-Verlag 1986: 149–60CrossRefGoogle Scholar
  14. 14.
    MacLaughlin M, de Mello Aires M, Malmic G. Verapamil effect on renal function in normotensive and hypertensive rats. Renal Physiol 1985; 8: 112–9.PubMedGoogle Scholar
  15. 15.
    MacGregor GA, Pevahouse J, Capuccio F, et al. Nifedipine, diuretics and sodium balance. J Hypertens 1987; 5 Suppl. 4: S127–31.CrossRefGoogle Scholar
  16. 16.
    Ruilope LM, Miranda B, Oliet A, et al. Persistence of the natriuretic effect of calcium entry blockers. J Cardiovasc Pharmacol 1988; 12 Suppl. 4: S136–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Luckhaus G, Garthoff B, Kazda S. Prevention of hypertensive vasculopathy by nifedipine in salt loaded Dahl rats. Arzneimittelforschung 1982; 32: 1421–5.PubMedGoogle Scholar
  18. 18.
    Sraka M. Doctoral thesis. University of Heidelberg, in press, 1994Google Scholar
  19. 19.
    Fleckenstein A, Frey M, Zorn J, Fleckenstein-Grün G. Calcium, a neglected key factor in hypertension and arteriosclerosis. In: Laragh & Brenner, editors. Hypertension: pathophysiology, diagnosis, and management. New York: Raven Press Ltd 1990: 471–509Google Scholar
  20. 20.
    Kazda S, Garthoff B, Luckhaus G. Calcium antagonists in hypertensive disease: experimental evidence for a new therapeutic concept. Postgrad Med J 1983; 59 Suppl. 2: 78–83.PubMedGoogle Scholar
  21. 21.
    Luckhaus G, Nash G, Garthoff B, et al. Healing of malignant hypertensive arteriopathy in Dahl rats by nifedipine. Arzneimittelforschung 1985; 35: 115–21.PubMedGoogle Scholar
  22. 22.
    Kazda S. The calcium channel and vascular injury. In: Morad et al. editors. The calcium channel: structure, function and implications. Berlin: Springer-Verlag 1988: 326–34CrossRefGoogle Scholar
  23. 23.
    Frey M, von Witzleben H, Keidel A, et al. Restriction of Caoverload of the arterial walls of SHR by Ca antagonists (verapamil, nifedipine) [abstract]. Naunyn-Schmiedebergs Arch Pharmacol 1980; 313 Suppl.: R48.Google Scholar
  24. 24.
    Arnold-Schmiebusch H, Redlinger K, Christ B, et al. Elektronmikroskopisch-morphometrische Analyse der Gefaβwand von Koronaraterien bei SHR nach Behandlung mit dem Calcium-Antagonisten Nitrendipin. Verhandlungen der Deutschen Anatomisch Gesellschaft, 1993Google Scholar
  25. 25.
    Safar ME, Pannier B, Laurent S, et al. Calcium entry blockers and arterial compliance in hypertension. J Cardiovasc Pharmacol 1989; 14 Suppl. 10: S1–6.PubMedGoogle Scholar
  26. 26.
    Nilsson J, Sjölund M, Palmberg L, et al. The calcium angtagonist nifedipine inhibits arterial smooth muscle proliferation. Atherosclerosis 1985; 58: 109–22.PubMedCrossRefGoogle Scholar
  27. 27.
    Moolenaar WH, Tertoolen LGL, de Laat SW. Growth factors immediately raise cytoplasmic free calcium in human fibro-blasts J Biol Chem 1984; 259: 8066.PubMedGoogle Scholar
  28. 28.
    Hirata Y, Takagi Y, Fukuda Y, et al. Endothelin is a potent mitogen for rat vascular smooth muscle. Atherosclerosis 1989; 78: 225–8.PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1994

Authors and Affiliations

  • S. Kazda
    • 1
  1. 1.Department of HypertensionBayer AG, Pharma Reseach Centre, Institute for Cardiovascular and Arteriosclerosis ResearchWuppertalGermany

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