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Rationale for Combined Therapy with Calcium Antagonists and Ace Inhibitors

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Pharmacological Control of Calcium and Potassium Homeostasis

Part of the book series: Medical Science Symposia Series ((MSSS,volume 9))

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Abstract

Atherosclerosis is the major cause for cardiovascular diseases, including myocardial infarction and stroke, responsible for about 50% of total mortality in Europe, the United States, and Japan. The formation of the atherosclerotic lesion is a multifactorial process that involves several mechanisms: endothelial damage; lipid accumulation in the intimai tissue of the arterial vessel; smooth muscle cell proliferation and migration from the medial layer to the intimal layer of the artery; and synthesis and accumulation of proteoglycans and other components of the extracellular matrix [1]. Several growth factors including cytokines and vasoactive molecules are also involved in the atherosclerotic lesion formation [1]. These factors can be synthesized by the different cell types involved in the atherosclerotic process: endothelial cells, smooth muscle cells, macrophages, and platelets [1].

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References

  1. Ross R. The pathogenesis of atherosclerosis: A perspective for the 1990s. Nature 1993;362:801–809.

    Article  PubMed  CAS  Google Scholar 

  2. Ross R. The pathogenesis of atherosclerosis - An update. New Engl J Med 1986; 314:488–500.

    Article  PubMed  CAS  Google Scholar 

  3. Brown MS, Goldstein JL. Lipoprotein metabolism in the macrophage: Implications for cholesterol deposition in atherosclerosis. Ann Rev Biochem 1983;52:223–261.

    Article  PubMed  CAS  Google Scholar 

  4. Mahley RW, Innerarity TL, Weisgraber KH, Oh SY. Altered metabolism (in vivo and in vitro) of plasma lipoproteins after selective chemical modification of lysine residues of the apoproteins. J Clin Invest 1979;64:743–750.

    Article  PubMed  CAS  Google Scholar 

  5. Witzum JL, Steinberg D. Role of oxidized low-density lipoprotein in atherogenesis. J Clin Invest 1991;88:1785–1792.

    Article  Google Scholar 

  6. Roma P, Catapano AL, Bertulli SM, Varesi L, Fumagalli R, Bernini F. Oxidized LDL increase free cholesterol and fail to stimulate cholesterol esterification in murine macrophages. Biochem Biophys Res Commun 1990;171:123–131.

    Article  PubMed  CAS  Google Scholar 

  7. Brown MS, Goldstein JL, Krieger M, Ho Y, Anderson R. Reversible accumulation of cholesteryl esters in macrophages incubated with acetylated lipoproteins. J Cell Biol 1979;82:597–613.

    Article  PubMed  CAS  Google Scholar 

  8. Schwartz SM, Campbell GR, Campbell JH. Replication of smooth muscle cells in vascular disease. Circ Res 1986;58:427–444.

    Article  Google Scholar 

  9. Campbell GR, Campbell JH, Manderson JA, Horrigan S, Rennick RE. Arterial smooth muscle. A multifactorial mesenchymal cell. Arch Pathol Lab Med 1988; 112:977–986.

    PubMed  CAS  Google Scholar 

  10. Weinstein DB, Heider JG. Antiatherogenic properties of calcium-antagonists. Am J Cardiol 1987;59:163B–172B.

    Article  PubMed  CAS  Google Scholar 

  11. Sowers JR. Calcium channel blockers and atherosclerosis. Am J Kid Dis 1990;XVI:3–9.

    Google Scholar 

  12. Lichtlen PR, Hugenholtz PG, Hecker H, Jost S, Deckers JW. Retardation of angiographic progression of coronary artery disease by nifedipine, Results of international nifedipine trial on atherosclerotic therapy (INTACT). Lancet 1990;335:1109–1113.

    Article  PubMed  CAS  Google Scholar 

  13. Nomoto A, Mutoh S, Hagihara H, Yamaguchi I. Smooth muscle cell migration induced by inflammatory cell products and its inhibition by a potent calcium antagonist, nilvadipine. Atherosclerosis 1988;72:213–219.

    Article  PubMed  CAS  Google Scholar 

  14. Leiter LA. Regression of atherosclerosis. Can Med Assoc J 1991;144:459.

    CAS  Google Scholar 

  15. Bernini F, Fantoni M, Corsini A, Fumagalli R. In vitro inhibition of arterial myocyte growth and stimulation of low density lipoprotein metabolism by SIM 6080, a new calcium antagonist. Pharm Res 1990;22:27–35.

    Article  CAS  Google Scholar 

  16. Bernini F, Bellosta S, Didoni G, Fumagalli R. Calcium antagonists and cholesteryl ester metabolism in macrophages. J Cardiovasc Pharmacol 1991;18(Supp1.10): S42–S45.

    Google Scholar 

  17. Bernini F, Catapano AL, Corsini A, Fumagalli R, Paoletti R. Effects of calcium antagonists on lipids and atherosclerosis. Am J Cardiol 1989;64:129I–133I.

    Article  PubMed  CAS  Google Scholar 

  18. Heider JG, Weinstein DB, Pickens CE, Lan S, Su C-M. Antiatherogenic activity of the calcium channel blockers isradipine (PN 200–110): A novel effect on matrix synthesis independent of calcium channel blockade. Transplant Proc 1987;4:96–101.

    Google Scholar 

  19. Raiteri M, Corsini A, Soma MR, et al. Antiatherosclerotic drugs: A critical assessment. In: Catapano AL, Gotto AM Jr., Smith LC, Paoletti R, editors. Drugs Affecting Lipid Metabolism. Dordrecht:Kluwer Academic Publishers, 1993:317–331.

    Google Scholar 

  20. Corsini A, Raiteri M, Soma MR, Fumagalli R, Paoletti R. Simvastatin but not pravastatin inhibits the proliferation of rat aorta myocytes. Pharm Res 1991;23:173–180.

    Article  CAS  Google Scholar 

  21. Corsini A, Mazzotti M, Raiteri M, et al. Relationship between mevalonate pathway and arterial myocyte proliferation: in vitro studies with inhibitors of HMG-CoA reductase. Atherosclerosis 1993;101:117–125.

    Article  PubMed  CAS  Google Scholar 

  22. Bernini F, Didoni G, Bonfadini G, Bellosta S, Fumagalli R. Requirement for mevalonate in acetylated LDL induction of cholesterol esterification in macrophages. Atherosclerosis 1993;104:19–26.

    Article  PubMed  CAS  Google Scholar 

  23. Soma MR, Donetti E, Parolini C, Mazzini G, Ferrari C, Fumagalli R, Paoletti R. HMGCoA reductase inhibitors: In vivo effects on intimai carotid thickening in rabbits. Arterioscl Thromb 1993;13:571–578.

    Article  PubMed  CAS  Google Scholar 

  24. Henry PD, Bentley KI. Suppression of atherogenesis in cholesterol-fed rabbit treated with nifedipine. J Clin Invest 1981;68:1366–1369.

    Article  PubMed  CAS  Google Scholar 

  25. Weinstein DB, Heider JG. Antiatherogenic properties of calcium antagonists: state of the art. Am J Med 1989;86(Suppl.4A):27–32.

    Article  PubMed  CAS  Google Scholar 

  26. Maggi FM, Bernini F, Barberi L, Fantoni M, Catapano AL. SIM 6080, a new calcium antagonist, reduces aortic atherosclerosis in cholesterol-fed rabbits. Pharm Res 1993;28:219–227.

    Article  CAS  Google Scholar 

  27. Skepper JN, Kappagoda CT. The effect of concurrent administration of isradipine on the development of fatty streaks in the cholesterol-fed rabbit: A morphometric study. Atherosclerosis 1992;96:17–31.

    Article  PubMed  CAS  Google Scholar 

  28. Chobanian AV, Haudenschild CC, Nickerson C, Drago R. Antiatherogenic effect of captopril in the Watanabeh heritable hyperlipidemic rabbit. Hypertension 1990; 15:327–331.

    Article  PubMed  CAS  Google Scholar 

  29. Aberg G, Ferrer P. Effects of captopril on atherosclerosis in cynomologous monkeys. J Cardiovasc Pharmacol 1990;15 (Suppl.5):S65–S72.

    PubMed  CAS  Google Scholar 

  30. Capron L, Heudes D, Chajara A, Bruneval P. Effect of ramipril, an inhibitor of angiotensin converting enzyme, on the response of rat thoracic aorta to injury with a balloon catheter. J Cardiovasc Pharmacol 1991;18:207–211.

    Article  PubMed  CAS  Google Scholar 

  31. Powell JS, Clozel JP, Muller RKM, et al. Inhibitors of angiotensin-converting enzyme prevent myointimal proliferation after vascular injury. Science 1989;245: 186–188.

    Article  PubMed  CAS  Google Scholar 

  32. Clowes AW, Clowes MM, Vergel SC,et al. Heparin and cilazapril together inhibit injury-induced intimai hyperplasia. Hypertension 1991;18:65–69.

    Article  Google Scholar 

  33. Lam JYT, Lacoste L, Bourassa MG. Cilazapril and early atherosclerotic changes after balloon injury of porcine carotid arteries. Circulation 1992;85:1542–1547.

    Article  PubMed  CAS  Google Scholar 

  34. Roux SP, Clorel JP, Kuhn H. Cilazapril inhibits wall thickening of vein bypass graft in the rat. Hypertension 1991;18:43–46.

    Article  Google Scholar 

  35. The Multicenter European Research Trial with Cilazapril after Angioplasty to Prevent Transluminal Coronary Obstruction and Restenosis (MERCATOR) Study Group. Does the new angiotensin converting enzyme inhibitor cilazapril prevent restenosis after percutaneous transluminal coronary angioplasty? Results of the MERCATOR study: a multicenter, randomized, double-blind placebo-controlled trial. Circulation 1992;86:100–110.

    Article  Google Scholar 

  36. Kauffman RF, Bean JS, Zimmermann KM, Brown RF, Steinberg MI. Losartan, a nonpeptide angiotensin-II (ANG-II) receptor antagonist, inhibits neointima formation following balloon injury to rat carotid arteries. Life Sci 1991;49:L223–L228.

    Article  Google Scholar 

  37. Finta KM, Fischer MJ, Lee L, Gordon D, Pitt B, Webb RC. Ramipril prevents impaired endothelium-dependent relaxation in arteries from rabbits fed an atherogenic diet. Atherosclerosis 1993;100:149–156.

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Institute of Pharmacological Sciences, University of Milan, 20133, Via Balzaretti 9, Milan, ITALY

    Rodolfo Paoletti

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  1. Rodolfo Paoletti
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Editor information

Editors and Affiliations

  1. Laboratory of Pharmacology, Catholic University of Louvain, Brussels, Belgium

    T. Godfraind

  2. Center of Physiology, Hypertension Clinic, University of Milan, Milan, Italy

    G. Mancia

  3. Institute of Pharmacological Sciences, University of Milan, Milan, Italy

    M. P. Abbracchio

  4. Baylor College of Medicine, Houston, Texas, USA

    L. Aguilar-Bryan

  5. Institute of Pharmacology, University of Pavia, Pavia, Italy

    S. Govoni

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© 1995 Springer Science+Business Media Dordrecht

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Paoletti, R. (1995). Rationale for Combined Therapy with Calcium Antagonists and Ace Inhibitors. In: Godfraind, T., Mancia, G., Abbracchio, M.P., Aguilar-Bryan, L., Govoni, S. (eds) Pharmacological Control of Calcium and Potassium Homeostasis. Medical Science Symposia Series, vol 9. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-0117-2_18

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  • DOI: https://doi.org/10.1007/978-94-011-0117-2_18

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-4056-3

  • Online ISBN: 978-94-011-0117-2

  • eBook Packages: Springer Book Archive

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