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The Coronary Selectivity of Calcium Antagonists — Focus on CHD

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Abstract

Calcium ions play an essential role in the contractility of skeletal and smooth muscle and of both the normal and diseased heart. Calcium channel blockers (CCBs), also termed calcium antagonists, calcium entry blockers or more simply calcium blockers (in French, anticalciques), inhibit the inward movement of calcium in depolarised muscles. This calcium influx occurs through L-type (long-lasting, large-current, or slow), voltage-dependent calcium channels. This results in relaxation of vascular smooth muscle and reduction of cardiac contractility. Although belonging to different chemical families (Fig. 1.1), CCBs are often assumed to be a pharmacologically homogeneous family of drugs. The common property of CCBs is their capacity to relax calcium-evoked contraction of depolarised smooth muscle (Godfraind and Polster 1968; Godfraind and Kaba 1969). Refined pharmacological studies show that variations in chemical structure may result in differences in binding sites, tissue selectivity, and, consequently, clinical activity and therapeutic indications (Godfraind et al. 1986).

Keywords

Calcium Channel Calcium Channel Blocker Calcium Antagonist Cardiac Hypertrophy Internal Mammary Artery 
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. Böhm M, Schwinger RHG, Erdmann E (1990) Different cardiodepressant potency of various calcium antagonists in human myocardium. Am J Cardiol 65: 1039–1041PubMedCrossRefGoogle Scholar
  2. Boyd RA, Giacomini JC, Giacomini KM (1988) Species differences in the negative isotropic response of 1,4-dihydropyridine calcium channel blockers in myocardium. J Cardiovasc Pharmacol 12: 650–657PubMedCrossRefGoogle Scholar
  3. Cohn JN, Ziesche S, Smith R et al (1997) Effect of the calcium antagonist felodipine as supplementary vasodilator therapy in patients with chronic heart failure treated with enalapril: V-HeFT III. Vasodilator-Heart Failure Trial (V-HeFT) Study Group. Circulation 96 (3): 856–863PubMedGoogle Scholar
  4. Cristofori P, Terron A, Michelli D, Bertolini G, Gaviraghi G (1994) Lacidipine: experi- mental evidence of vasculoprotective properties. J Cardiovas Pharmacol 23: S90 - S93Google Scholar
  5. Feron O, Octave JN, Christen MO, Godfraind T (1994) Quantification of two splicing events in the L-type calcium channel al subunit of intestinal smooth muscle and other tissues. Eur J Biochem 222: 195–202PubMedCrossRefGoogle Scholar
  6. Feron O, Salomone S, Godfraind T (1996) Action of the calcium channel blocker lacidipine on cardiac hypertrophy and endothelin-1 gene expression in stroke-prone hypertensive rats. Br J Pharmacol 118 (3) 659–664PubMedGoogle Scholar
  7. Finet M, Godfraind T, Khoury G (1985) The positive inotropic action of a nifedipine analogue, Bay K 8644, in guinea-pig and rat isolated cardiac preparations. Br J Pharmacol 86: 27–32PubMedGoogle Scholar
  8. Godfraind T, Kaba A (1969) Blockade or reversal of contraction induced by calcium and adrenaline in depolarized arterial smooth muscle. Br J Pharmacol 36: 549–560PubMedGoogle Scholar
  9. Godfraind T, Polster P (1968) Etude comparative de médicaments inhibant la réponse contractile de vaisseaux isolés d’origine humaine ou animale. Thérapie 23: 1209–1220PubMedGoogle Scholar
  10. Godfraind T, Salomone S (1996) Calcium antagonists and endothelial function: focus on nitric oxide and endothelin. Cardiovasc Drugs Ther 10 (4): 439–446PubMedCrossRefGoogle Scholar
  11. Godfraind T, Salomone S (1997) New advances in hypertensive treatment with calcium antagonists. J Cardiovasc Pharmacol 30 (Suppl 2): S1 - S5Google Scholar
  12. Godfraind T (1994) Calcium antagonists and vasodilatation. Pharmacol Ther 64 (1): 3775CrossRefGoogle Scholar
  13. Godfraind T, Kaba A, Polster P (1966) Specific antagonism to the direct and indirect action of angiotensin on the isolated guinea-pig ileum. Br J Pharmacol Chemother 28: 93–104PubMedGoogle Scholar
  14. Godfraind T, Miller RC, Wibo M (1986a) Calcium antagonism and calcium entry blockade. Pharmacol Rev 38: 321–416PubMedGoogle Scholar
  15. Godfraind T, Morel N, Wibo M (1986b) The heterogeneity of calcium movements in cardiac and vascular smooth muscle cells. Scand J Clin Lab Invest 46 (Suppl 180): 29–40Google Scholar
  16. Godfraind T, Eglème C, Finet M, Jaumin P (1987) The actions of nifedipine and nisoldipine on the contractile activity of human coronary arteries and human cardiac tissue in vitro. Pharmacol Toxic 61: 79–84CrossRefGoogle Scholar
  17. Godfraind T, Morel N, Wibo M (1988) Tissue specificity of dihydropyridine-type calcium antagonists in human isolated tissues. Trends Pharmacol Sci 9: 37–39PubMedCrossRefGoogle Scholar
  18. Godfraind T, Kazda S, Wibo M (1991) Effects of a chronic treatment by nisoldipine, a calcium antagonistic dihydropyridine, on arteries of spontaneously hypertensive rats. Circ Res 68: 674–682PubMedGoogle Scholar
  19. Godfraind T, Dessy C, Salomone S (1992a) A comparison of the potency of selective L-calcium channel inhibitors in human coronary and internal mammary arteries exposed to serotonin. J Pharmacol Exp Ther 263: 112–122PubMedGoogle Scholar
  20. Godfraind T, Morel N, Salomone S (1992b) Characterization in human coronary arteries of the binding sites responsible for the pharmacologic action of amlodipine: a comparison with animal vascular tissues. J Cardiovasc Pharmacol 20 (Suppl A): S33 - S39Google Scholar
  21. Godfraind T, Salomone S, Dessy C, Verhelst B, Dion R, Schoevaerts JC (1992c) Selectivity scale of calcium antagonists in the human cardiovascular system (based on in vitro studies). J Cardiovasc Pharmacol 20 (Suppl 5): S34 - S41PubMedGoogle Scholar
  22. Hansen JF (1998) Is the safety and efficacy of calcium antagonists now established? Cardiovasc Drugs Ther 12: 145–147PubMedCrossRefGoogle Scholar
  23. Kaplan NM (1998a) Commentary on the sixth report of the Joint National Committee (JNC-6). Am J Hypertens 11 (1 Pt 1): 134–136PubMedGoogle Scholar
  24. Kaplan NM (1998b) The 6th joint national committee report (JNC-6): new guidelines for hypertension therapy from the USA. Keio J Med 47 (2): 99–105PubMedCrossRefGoogle Scholar
  25. Kazda S, Garthoff B, Meyer H, Schloßmann K, Stoepel K, Towart R, Vater W, Wehinger E (1980) Pharmacology of a new calcium antagonistic compound, isobutyl methyl 1,4 dihydro-2,6-demethyl-4-(2-nitrophenyl)-3,5-pyridinecarboxylate (nisoldipine, Bay k 5552). Arzneim Forsch 30: 2144–2162Google Scholar
  26. Kyselovic J, Morel N, Wibo M, Godfraind T (1998a) Prevention of salt-dependent cardiac remodeling and enhanced gene expression in stroke-prone hypertensive rats by the long-acting calcium channel blocker lacidipine. J Hypertens 16 (10): 1515–1522PubMedCrossRefGoogle Scholar
  27. Kyselovic J, Salomone S, Wibo M, Godfraind T (1998b) Effect of nifedipine on salt-dependent cardiac hypertrophy in stroke-prone spontaneously hypertensive rats. Br J Pharmacol 123: 320 PGoogle Scholar
  28. Leonetti G, Cuspidi C, Sampieri L, Terzoli L, Zanchetti A (1982) Comparison of cardiovascular, renal and humoral effects of acute administration of two calcium channel blockers in normotensive and hypertensive subjects. J Cardiovasc Pharmacol 4: S319 - S324PubMedCrossRefGoogle Scholar
  29. Mancia G, Grassi G (1997) Antihypertensive effects of combined lisinopril and hydrochlorothiazide in elderly patients with systodiastolic or systolic hypertension: results of a multicenter trial. J Cardiovasc Pharmacol 30 (5): 548–553PubMedCrossRefGoogle Scholar
  30. Mancia G, Grassi G (1998) Antihypertensive treatment: past, present and future. J Hypertens 16 (1): S1 - S7CrossRefGoogle Scholar
  31. Mancia G, Omboni S, Grassi G (1997a) Combination treatment in hypertension: the Vera Tran Study. Am J Hypertens 7 (Pt 2): 153S - 158SGoogle Scholar
  32. Mancia G, Sega R, Milesi C, Cesana G, Zanchetti A (1997b) Blood-pressure control in the hypertensive population Lancet 349 (9050): 454–457PubMedCrossRefGoogle Scholar
  33. Mathew V, Hasdai D, Lerman A (1996) The role of endothelin in coronary atherosclerosis. Mayo Clin Proc 71: 769–777PubMedCrossRefGoogle Scholar
  34. Messerli FH (1996) What, if anything, is controversial about calcium antagonists? Am J Hypertens l2 (Pt 2): 177S - 181SCrossRefGoogle Scholar
  35. Messerli FH, Schmieder RE, Weir MR (1997) Salt. A perpetrator of hypertensive target organ disease? Arch Intern Med 157: 2449–2452PubMedCrossRefGoogle Scholar
  36. Morel N, Godfraind T (1987) Prolonged depolarization increases the pharmacological effect of dihydropyridines and their binding affinity for calcium channel of vascular smooth muscle. J Pharmacol Exp Ther 243: 711–715PubMedGoogle Scholar
  37. Morel N, Godfraind T (1994) Selective interaction of the calcium antagonist amlodipine with calcium channels in arteries of spontaneously hypertensive rats. J Cardiovasc Pharmacol 24: 524–533PubMedCrossRefGoogle Scholar
  38. Morel N, Buryi V, Feron O, Gomez JP, Christen MO, Godfraind T (1998) The action of calcium channel blockers on recombinant L-type calcium channel al subunit. Br J Pharmacol 125: 1005–1012PubMedCrossRefGoogle Scholar
  39. Opie LH (1990) Clinical use of calcium channel antagonist drugs. 2nd edn. Kluwer, BostonGoogle Scholar
  40. Rossi GP et al (1999) Endothelin-1 and its mRNA in the wall layers of human arteries ex vivo. Circulation 99: 1147–1155PubMedGoogle Scholar
  41. Schwartzkopff B, Strauer BE (1999) Squeezing tubes: a case of remodeling and regulation: coronary reserve in hypertensive heart disease. Cardiovasc Res 40: 4–8CrossRefGoogle Scholar
  42. Spedding M, Fraser S, Clarke B, Patmore L (1990) Factors modifying the tissue selectivity of calcium antagonists. J Neural Transm 1. 5–16Google Scholar
  43. Wibo M, De Roth L, Godfraind T (1988) Pharmacologic relevance of dihydropyridine binding sites in membrane from rat aorta: kinetic and equilibrium studies. Circ Res 62: 91–96PubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1999

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