Adalat pp 197-202 | Cite as

Calcium Antagonists for the Treatment of Atherosclerosis

  • P. D. Henry
Conference paper

Abstract

Current information indicates that calcium antagonists exert antiatherosclerotic effects in animals fed high-fat diets [1–3]. In several studies, structurally disparate calcium antagonists including nifedipine [4], verapamil [5], and diltiazem [6] have been reported to suppress the formation of atherosclerotic lesions developing within weeks after the onset of cholesterol feeding. In addition, nifedipine has been shown to inhibit the progression of atherosclerosis in Rhesus monkeys maintained for 1 year on an atherogenic diet [7]. Two controlled clinical trails using quantitative coronary arteriography to monitor the progression of coronary atherosclerosis in patients with symptomatic ischemic heart disease have been recently completed [8, 9]. Results indicate that treatment with nifedipine [8] or nicardipine [9] suppresses the development of new or small occlusive lesions. These clinical reports have generated new interest in the study of calcium antagonists as antiatherogenic agents. Here, we review possible mechanisms by which calcium antagonists could exert their antiatherosclerotic effects.

Keywords

Cholesterol Cardiol Stein Propranolol Verapamil 

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References

  1. 1.
    Henry PD (1987) Anti-atherosclerotic effects of calcium antagonists: a brief review. Clin Invest Med 10:601–606PubMedGoogle Scholar
  2. 2.
    Henry PD (1988) Calcium antagonists as anti-atherogenic agents. Ann NY Acad Sci 522:411–419PubMedCrossRefGoogle Scholar
  3. 3.
    Henry PD (1990) Antiatherogenic effects of calcium channel blockers: possible mechanisms of action. Cardiovasc Drug Ther 4:1015–1020CrossRefGoogle Scholar
  4. 4.
    Henry PD, Bentley KI (1981) Suppression of atherogenesis in cholesterol-fed rabbit treated with nifedipine. J Clin Invest 68:1366–1369PubMedCrossRefGoogle Scholar
  5. 5.
    Rouleau JL, Parmely WW, Stevens J, Wilkman-Coffelt J, Sievers R, Mahley RW, Havel RJ (1983) Verapamil suppresses atherosclerosis in cholesterol-fed rabbits. J Am Coll Cardiol 1:1453–1460PubMedCrossRefGoogle Scholar
  6. 6.
    Ginsburg R, Davis K, Bristow MR, McKennett K, Kodsi SR, Billingham ME, Schroeder JS (1983) Calcium antagonists suppress atherogenesis in aorta but not in the intramural coronary arteries of cholesterol-fed rabbits. Lab Invest 49:154–158PubMedGoogle Scholar
  7. 7.
    Lichtor T, Davis HR, Vesselinovitch D, Wissler RW, Mullan S (1989) Suppression of atherogenesis by nifedipine in the cholesterol-fed Rhesus monkey. Appl Pathol 7:8–18PubMedGoogle Scholar
  8. 8.
    Lichtlen PR, Hugenholtz PG, Rafflenbeul W, Hecker H, Jost S, Deckers JW (1990) Retardation of angiographic progression of coronary artery disease by nifedipine. Results of International Nifedipine Trial on Anti-atherosclerotic Therapy (INTACT). Lancet 335:1109–1113PubMedCrossRefGoogle Scholar
  9. 9.
    Waters D, Lespérance J, Francetich M, Causey D, Théroux P, Chiang Y-K, Hudon G, Lemarbre L, Reitman M, Joyal M, Gosselin G, Dyrda I, Macer J, Havel RJ (1990) A controlled trial to assess the effect of a calcium channel blocker upon the progression of coronary atherosclerosis. Circulation 82:1940–1953PubMedCrossRefGoogle Scholar
  10. 10.
    Blumlein SL, Sievers R, Kidd P, Parmley WW (1984) Mechanism of protection from atherosclerosis by verapamil in the cholesterol-fed rabbit. Am J Cardiol 54:884–889PubMedCrossRefGoogle Scholar
  11. 11.
    Habib JB, Bossaller C, Well S, Williams C, Momsett JD, Henry PD (1986) Preservation of endothelium-dependent vascular relaxation in cholesterol-fed rabbit by treatment with the calcium blocker PN 200–110. Cire Res 58:305–309CrossRefGoogle Scholar
  12. 12.
    Willis AL, Nagel B, Churchill V, Whyte MA, Smith DL, Mahmud I, Puppione DL (1985) Antiatherosclerotic effects of nicardipine and nifedipine in cholesterol-fed rabbits. Arteriosclerosis 5:250–255PubMedCrossRefGoogle Scholar
  13. 13.
    Sugano N, Nashkashima Y, Matsushima T, Takahora K, Taksugi M, Kuroiwa A, Koide O (1986) Suppression of atherosclerosis in cholesterol-fed rabbits by diltiazem injection. Arteriosclerosis 6:237–241PubMedCrossRefGoogle Scholar
  14. 14.
    Ohata I, Sakamoto N, Nagano K, Maeno H (1984) Low density lipoprotein-lowering and high density lipoprotein-elevating effects of nicardipine in rats. Biochem Pharmacol 33:2199–2205PubMedCrossRefGoogle Scholar
  15. 15.
    Stein O, Leitersdorf E, Stein Y (1985) Verapamil enhances receptor-mediated endocytosis of low density lipoproteins by aortic cells in culture. Arteriosclerosis 5:35–44PubMedCrossRefGoogle Scholar
  16. 16.
    Corsini A, Fumagalli R, Paoletti R (1986) Calcium antagonists and low density lipoproteins metabolism by human fibroblasts and by human hepatoma cell line HEP G2. Pharmacol Res Commun 18:1–16PubMedGoogle Scholar
  17. 17.
    Etingin OR, Hajjar DP (1985) Nifedipine increases cholesteryl ester hydrolytic activity in lipid-laden rabbit arterial smooth muscle cells. J Clin Invest 75:1554–1558PubMedCrossRefGoogle Scholar
  18. 18.
    Etingin OR, Hajjar DP (1990) Calcium channel blockers enhance cholesteryl ester hydrolysis and decrease total cholesterol accumulation in human aortic tissue. Circ Res 66:185–190PubMedCrossRefGoogle Scholar
  19. 19.
    Schmitz G, Robenek H, Beuck M, Krause R, Schurek A, Niemann R (1988) Ca++ antagonists and ACAT inhibitors promote cholesterol efflux from macrophages by different mechanisms. Arteriosclerosis 8:46–56PubMedCrossRefGoogle Scholar
  20. 20.
    Moore JB, Fuller BL, Falotico R, Toman EL (1985) Inhibition of rabbit platelet phosphodiesterase activity and aggregation by calcium channel blockers. Thromb Res 40:401–411PubMedCrossRefGoogle Scholar
  21. 21.
    Hiroki T, Morishita Y, Inoue T, Yoshida T, Arakawa K (1985) Effect of nifedipine on platelet aggregation response to exercise in patients with ischaemic heart disease. In: Lichtlen PR (ed) 6th International Adalat Symposium, Excerpta Medica, Amsterdam, pp. 504–507Google Scholar
  22. 22.
    Betz E (1988) The effect of calcium antagonists on intimal cell proliferation in atherogenesis. Ann NY Acad Sci 522:399–410PubMedCrossRefGoogle Scholar
  23. 23.
    Tedgui A, Chiron B, Curmi P, Juan L (1987) Effect of nicardipine and verapamil on in vitro albumin transport in rabbit thoracic aorta. Arteriosclerosis 7:80–87PubMedCrossRefGoogle Scholar
  24. 24.
    Nakao J, Ito H, Ooyama T, Chang WC, Murota S (1983) Calcium dependency of aortic smooth muscle cell migration induced by 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid. Atherosclerosis 46:309–319PubMedCrossRefGoogle Scholar
  25. 25.
    Nomoto A, Hirosumi J, Sekiguchi C, Mutoh S, Yamaguchi I, Aoki H (1987) Antiatherogenic acitivity of FR34235 (nilvadipine), a new potent calcium antagonist. Atherosclerosis 64:255–261PubMedCrossRefGoogle Scholar
  26. 26.
    Janero DR, Burghardt B, Lopez R (1988) Protection of cardiac membrane phospholipid against oxidative injury by calcium antagonists. Biochem Pharmacol 37:4197PubMedCrossRefGoogle Scholar
  27. 27.
    Mak IT, Weglicki WB (1990) Comparative antioxidant activities of propranolol, nifedipine, verapamil and diltiazem against sarcolemmal membrane lipid peroxidation. Circ Res 66:1449PubMedCrossRefGoogle Scholar
  28. 28.
    Ondrias K, Misik V, Gerbel D, Stasko A (1989) Lipid peroxidation of phosphatidylcholine liposomes depressed by calcium channel blockers nifedipine and verapamil and by the antiarrhythmic-antihypoxic drug stobadine. Biochim Biophys Acta 1003:238PubMedCrossRefGoogle Scholar
  29. 29.
    Stein O, Halperin G, Stein Y (1987) Long-term effects of verapamil on aortic smooth muscle cells cultured in the presence of hypercholesterolemic serum. Arteriosclerosis 7:585–592PubMedCrossRefGoogle Scholar
  30. 30.
    Jackson LJ, Bush RC, Bowyer DE (1988) Inhibitory effect of calcium antagonists on balloon catheter-induced arterial smooth muscle cell proliferation and lesion size. Atherosclerosis 69:115–122PubMedCrossRefGoogle Scholar
  31. 31.
    Hirosumi J, Nomoto A, Ohkubo Y et al. (1988) Inflammatory responses in cuff-induced atherosclerosis in rabbit. Atherosclerosis 64:243–254CrossRefGoogle Scholar
  32. 32.
    Weinstein DB, Heider JG (1987) Antiatherogenic properties of calcium antagonists. Am J Cardiol 59:163B-172BPubMedCrossRefGoogle Scholar
  33. 33.
    Fleckenstein A (1983) Calcium antagonism in heart and smooth muscle. Wiley, New York, pp. 272–279Google Scholar
  34. 34.
    Mutoh S, Nomoto A, Sekiguchi C, Yamaguchi I (1988) Protective action of a calcium antagonist, nilvadipine, against aortic calcium deposition — a pathogenic factor in atherosclerosis. Atherosclerosis 73:181–189PubMedCrossRefGoogle Scholar
  35. 35.
    Stary H (1985) Macrophage foam cells in the coronary artery intima of human infants. Ann NY Acad Sci 454:5–8PubMedCrossRefGoogle Scholar
  36. 36.
    Henry PD, Perez JE (1984) Clinical pharmacology of calcium antagonists. In: Conti CR (ed) Cardiac drug therapy. Davis, Philadelphia, pp. 93–109Google Scholar
  37. 37.
    Henry PD (1984) Calcium antagonists as antiatherogenic agents. In: Opie LH (ed) Calcium antagonists and cardiovascular disease. Raven, New York, pp. 209–213Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1991

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  • P. D. Henry

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