Do calcium antagonists inhibit atherogenesis?

  • P. Pauletto
  • G. Scannapieco


In the last few years calcium antagonists have been reported to act as antiatherosclerotic agents independently from any modification of risk factors. Since these compounds have no adverse effect on plasma lipoproteins profile and are effective antihypertensives, they may represent first-line drugs in this field. However, contrasting results are reported in the literature on the antiatherogenic effect of calcium antagonists in experimental animals, and only preliminary data exist on the effect in humans. This paper summarizes the main in vivo and in vitro studies so far conducted in this field and focuses on the mechanisms by which calcium antagonists may exert their antiatherosclerotic action.


Calcium Antagonist Atherosclerotic Lesion Cholesterol Diet Aortic Atherosclerosis Antiatherogenic Effect 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1).
    Opie LH. Calcium antagonists. Mechanisms, therapeutic indications and reservations: a review. Quart J Med 1984; New Series LIII/209:1–16.Google Scholar
  2. 2).
    Henry PD, Bentley KI. Suppression of atherogenesis in cholesterol-fed rabbit treated with nifedipine. J Clin Invest 1981; 68: 1366–1369.CrossRefPubMedGoogle Scholar
  3. 3).
    Willis AL, Nagel B, Churchill V et al. Antiatherosclerotic effect of nicardipine and nifedipine in cholesterol-fed rabbits. Arteriosclerosis 1985; 5: 250–255.CrossRefPubMedGoogle Scholar
  4. 4).
    Overturf ML, Smith SA. Failure of a high therapeutic dosage of nifedipine to suppress atherogenesis in cholesterol-fed rabbits. Arteriosclerosis 1982; 2: A408.Google Scholar
  5. 5).
    Stender S, Stender I, Nordestgaard B, Kjedsen K. No effect of nifedipine on atherogenesis in cholesterol-fed rabbits. Arteriosclerosis 1984; 4: 389–394.CrossRefPubMedGoogle Scholar
  6. 6).
    Ohata I, Sakamoto N, Nagano K, Maeno H. Low density lipoprotein-lowering and high density lipoprotein-elevating effects of nicardipine in rats. Pharmacol 1984; 33: 2199–2205.Google Scholar
  7. 7).
    Kritchevsky D, Tepper SA, Klurfeld DM. Flordipine, a calcium channel blocker, which does not influence lipidemia or atherosclerosis in cholesterol-fed rabbits. Atherosclerosis 1988; 69: 89–92.CrossRefPubMedGoogle Scholar
  8. 8).
    Overturf ML, Sybers H, Schaper J, Taegtmayer H. Hypertension and atherosclerosis in cholesterol-fed rabbits.II. One kidney-one clip Goldblatt hypertension treated with nifedipine. Atherosclerosis 1987; 66: 68–73.CrossRefGoogle Scholar
  9. 9).
    Thiery J, Niedmann PD, Seidel D. The beneficial influence of nifedipine on the regression of the cholesterol-induced atherosclerosis in rabbits. Exptl Med 1987; 187: 359–376.Google Scholar
  10. 10).
    Pauletto P, Sartore S, Scannapieco G et al. Immunocytochemical analysis of myosin isoform distribution in the atherosclerotic lesions of cholesterol-fed rabbits. In: Hypertension and Atherosclerosis, C Dal Palu’, R Ross, eds., Excerpta Medica, 1989: 107–112.Google Scholar
  11. 11).
    Pauletto P, Sartore S, Borrione A C et al. A nifedipine-sensitive smooth muscle cell subpopulation in the aortic media of hypercholesterolemic rabbit.X International Symposium on drugs affecting lipid metabolism.November 8–11, 1989 Houston, Texas, (abstract )Google Scholar
  12. 12).
    Lichtlen PB, Hugenholtz PG, Rafflenbeul W, Jost S, and the INTACT Study Group. Retardation of the progression of coronary artery disease in man by nifedipine; the international nifedipine trial on antiatherosclerotic therapy, in: Focus on Adalat.Google Scholar
  13. 13).
    Handley DA, Van Valen RG, Melden MK, Saunders RN. Suppression of rat carotid lesion development by the calcium channel blocker PN-200-110. Am J Pathol 1986; 124: 88–93.PubMedGoogle Scholar
  14. 14).
    Habib JB, Bossaller C, Wells S. Preservation of endothelium-dependent vascular relaxation in Cholesterol-fed rabbits by treatment with calcium blocker PN-200-110. Circ Res 1986; 58: 305 309.Google Scholar
  15. 15).
    Rouleau JL, Parmley WW, Stevens J et al. Verapamil suppresses atherosclerosis in cholesterol-fed rabbits. J Am Coll Cardiol 1983; 1 (6): 1453–1460.CrossRefPubMedGoogle Scholar
  16. 16).
    Blumstein SL, Sievers R, Kidd P, Parmley WW. Mechanism of protection from atherosclerosis by verapamil in the cholesterol-fed rabbit. Am J Cardiol 1984; 54: 884–889.CrossRefGoogle Scholar
  17. 17).
    Sugano M, Nakashima Y, Matsuchima T et al. Suppression of atherosclerosis in cholesterol-fed rabbits by diltiazem injections. Arteriosclerosis 1986; 6: 237–241.CrossRefPubMedGoogle Scholar
  18. 18).
    Ginsberg R, Davis K, Bristow MR et al. Calcium antagonists suppress atherogenesis in aorta but not in the intramural coronary arteries of cholesterol-fed rabbits. Lab Invest 1983; 9: 154–158.Google Scholar
  19. 19).
    Naito M, Kuzuya F, Asai K et al. Ineffectiveness of Ca++ antagonists nicardipine and diltiazem on experimental atherosclerosis in cholesterol-fed rabbits. Atherosclerosis 1984; 51: 343–344.CrossRefPubMedGoogle Scholar
  20. 20).
    Nilsson J, Sjolund M, Palmerg L et al. The calcium antagonist nifedipine inhibits arterial smooth muscle cell proliferation. Atherosclerosis, 1985; 58: 109–122.CrossRefPubMedGoogle Scholar
  21. 21).
    Nomoto A, Hirosumi J, Sekiguchi C et al. Antiatherogenic activity of FR34235 (Nilvadipine), a new potent calcium antagonist. Atherosclerosis, 1987; 64: 255–261.CrossRefPubMedGoogle Scholar
  22. 22).
    Schmitz G, Robenek H, Beuck M et al. Ca++ antagonist and ACAT inhibitors promote cholesterol efflux from macrophages by different mechanisms. Arteriosclerosis, 1988; 8: 46–56CrossRefPubMedGoogle Scholar
  23. 23).
    Robenek H and Schmitz G. Ca++ antagonist and ACAT inhibitors promote cholesterol efflux from macrophages by different mechanisms.II. Arteriosclerosis, 1988; 8: 57–67CrossRefPubMedGoogle Scholar
  24. 24).
    Stein O, Leitersdorf E, Stein Y. Verapamil enhances receptor-mediated endocytosis of low-density lipoproteins by aortic cells. Arteriosclerosis, 1985; 5: 35–44.CrossRefPubMedGoogle Scholar
  25. 25).
    Stein O, Halperin G, Stein Y. Long-term effects of verapamil on aortic smooth muscle cells cultured in the presence of hypercholesterolemic serum. Arteriosclerosis, 1987; 7: 585–592.CrossRefPubMedGoogle Scholar
  26. 26).
    Orekhov A, Tertov V, Khashimov K et al. Evidence of antiatherosclerotic action of verapimil from direct effects on arterial cells. Am J Cardiol 1987; 59: 495–496.CrossRefPubMedGoogle Scholar
  27. 27).
    Pauletto P, Angelini A, Vescovo G et al. The surface measurement of aortic atherosclerosis: critical survey and comparison with histologic findings. Int J Cardiol 1985; 8: 361–373.CrossRefPubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1990

Authors and Affiliations

  • P. Pauletto
    • 1
  • G. Scannapieco
    • 1
  1. 1.Clinica Medica IUniversità di PadovaItaly

Personalised recommendations