Calcium Channel Blockers in the Treatment of Hypertension

  • P. Weidmann
  • M. P. Gnaedinger
  • D. E. Uehlinger
Conference paper


The central role that calcium (Ca) plays in cardiovascular regulation is well apparent in several clinical situations. Chronic hypercalcemia due to hyperparathyroidism, vitamin C intoxication, or other etiologies is sometimes accompanied by hypertension [1]. Acute hypercalcemia induced by Ca infusion may also increase blood pressure (BP), particularly in patients with impaired renal function [2, 3]. Conversely, acute severe hypocalcemia causes hypotension [4], and a pharmacologic inhibition of transmembranous Ca transport has been noted to lower BP in various forms of hypertension [5–7, 8]. Ca antagonists, as they were termed by their scientific godfather Fleckenstein [9], or calcium channel blockers (CCB), the term in use more recently [10], are agents that inhibit the cellular entry of calcium through a broad group of voltage-dependent and receptor-operated, Ca,-selective plasma membrane ion channels [11, 12].


Essential Hypertension Calcium Channel Blocker Calcium Antagonist Plasma Renin Plasma Norepinephrine 
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.
    Weidmann P (1983) Essential, renal and endocrine hypertension. In: Massry SG, Glassock RJ (eds) Textbook of nephrology, vol 2. Williams and Wilkins, Baltimore, pp 6. 38–7. 382Google Scholar
  2. 2.
    Weidmann P, Massry SG, Coburn JW, Maxwell MH, Atleson J, Kleeman CR (1972) Blood pressure effects of acute hypercalcemia. Studies in patients with chronic renal failure., Ann Intern Med 76: 741–745PubMedGoogle Scholar
  3. 3.
    Marone C, Beretta-Piccoli C, Weidmann P (1980) Acute hypercalcemic hypertension in man: role of hemodynamics, catecholamines and renin. Kidney Int 20: 92–96CrossRefGoogle Scholar
  4. 4.
    Llach F, Weidmann P, Reinhart R, Maxwell MH, Coburn JW, Massry SG (1974) Effect of acute and long-standing hypocalcemia on blood pressure and plasma renin activity in man. J Clin Endocrinol Metab 38: 841–847PubMedCrossRefGoogle Scholar
  5. 5.
    Aoki K, Yoshida T, Kato S, Tazumi K, Sato I, Takikawa K, Hotta K (1976) Hypotensive action and increased plasma renin activity by Ca2+-antagonist (nifedipine) in hypertensive patients. Jpn Heart J 17: 479–484PubMedCrossRefGoogle Scholar
  6. 6.
    Lewis GRJ, Morley KD, Lewis BM, Bones PJ (1978) The treatment of hypertension with verapamil. NZ Med J 87: 351–354Google Scholar
  7. 7.
    Pedersen OL, Mikkelsen E, Christensen NJ, Kornerup HJ, Pedersen EB (1979) Effect of nifedipine on plasma renin, aldosterone and catecholamines in arterial hypertension. Eur J Clin Pharmacol 15: 235–240PubMedCrossRefGoogle Scholar
  8. 8.
    Olivari MT, Bartorelli C, Polese A, Fiorentini C, Moruzzi P, Guazzi MD (1979) Treatment of hypertension with nifedipine, a calcium antagonistic agent. Circulation 59: 1056–1062PubMedGoogle Scholar
  9. 9.
    Fleckenstein A (1983) Calcium antagonism in heart and smooth muscle. Experimental facts and therapeutic prospects., Wiley, New YorkGoogle Scholar
  10. 10.
    Katz AM, Reuter H (1979) Cellular calcium and cardiac cell death. Am J Cardiol 44: 188–190PubMedCrossRefGoogle Scholar
  11. 11.
    Katz AM, Hager WD, Messineo FC, Pappano A J (1984) Cellular actions and pharmacology of the calcium channel blocking drugs. Am J Med 77: 2–10PubMedGoogle Scholar
  12. 12.
    Antman EM, Stone PH, Mueller JE, Braunwald E (1980) Calcium channel blocking agents in the treatment of cardiovascular disorders: I. Basic and clinical electrophysiologic effects. Ann Intern Med 93: 875–885PubMedGoogle Scholar
  13. 13.
    Weidmann P, Gerber A, Laederach K (1984) Calcium antagonists in the treatment of hypertension: a critical overview. In: Crosnier J, Maxwell MH (eds) Advances in nephrology. Year Book Medical Publishers, Chicago, pp 197–232Google Scholar
  14. 14.
    Bianchetti MG, Beretta-Piccoli C, Weidmann P, Link L, Boehringer K, Ferrier C, Morton JJ (1983) Calcium and blood pressure regulation in normal and hypertensive subjects. Hypertension [Suppl 2] 5: II-57–II-65Google Scholar
  15. 15.
    Park CS, Han DS, Fray JCS (1981) Calcium in the control of renin secretion: Ca++ influx as an inhibitory signal. Am J Physiol 240: F70–F74PubMedGoogle Scholar
  16. 16.
    Oehmar H, Kubo S, Masaoka S, Kanazawa I, Yuasa A, Tsuchioka Y, Matsuura H, Kurogane H, Kajiyama G (1983) Sympathetic nerve and hormonal responses to a single dose of nifedipine in patients with essential hypertension and normal subjects: comparison among renin sub-groups. Hiroshima J Med Sci 32: 187–197Google Scholar
  17. 17.
    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 nor-motensive and hypertensive subjects. J Cardiovasc Pharmacol [Suppl 3] 4: 319s–324sCrossRefGoogle Scholar
  18. 18.
    Kiowski W, Bertel O, Erne P, Bolli P, Hulthen UL, Ritz R, Bühler F (1983) Hemodynamics and reflex response to acute and chronic antihypertensive therapy with the calcium entry blocker nifedipine. Hypertension [Suppl 1] 5: I-70–I-74Google Scholar
  19. 19.
    Corea L, Miele N, Bentivoglio E, Agabiti-Rosei E, Muiesan G (1979) Acute and chronic effects of nifedipine on plasma renin activity and plasma adrenaline and noradrenaline in controls and hypertensive patients. Clin Sci 57: 115s–117sPubMedGoogle Scholar
  20. 20.
    Corea L, Alunni G, Bentivoglio M, Boschetti E, Cosmi F, Giaimo MD, Miele N, Motolese M (1980) Acute and long-term effects of nifedipine on plasma renin activity and plasma catechol-amines in controls and hypertensive patients before and after metoprolol. Acta Ther 6: 177–189Google Scholar
  21. 21.
    Muiesan G, Agabiti-Rosei E, Alicandri C, Beschi M, Castellano M, Corea L, Fariello R, Romanelli G, Pasini C, Platto L (1981) Influence of verapamil on catecholamines, renin and aldosterone in essential hypertension patients. In: Zanchetti A, Krikler D (eds) Proceedings of the international symposium on calcium antagonism in cardiovascular therapy. Excerpta Medica, Amsterdam, p 238Google Scholar
  22. 22.
    Muiesan G, Agabiti-Rosei E, Castellano M, Alicandri CL, Corea L, Fariello R, Beschi M, Romanelli G (1982) Antihypertensive and humoral effects of verapamil and nifedipine in essential hypertension. J Cardiovasc Pharmacol [Suppl 3] 4: s325–s329PubMedCrossRefGoogle Scholar
  23. 23.
    Slike B, Ahuja RC, Okoli C, Nelson GIC, Taylor SH (1983) Blockade of slow calcium channels and regulation of circulatory pressor responses in uncomplicated hypertension. Isr J Med Sci 152: 364–372CrossRefGoogle Scholar
  24. 24.
    Corea L, Bentivoglio M, Cosmi F, Alunni G, Carnovali M (1981) Nifedipine versus prazosin in essential hypertension: a double-blind study. Curr Ther Res 30: 708–717Google Scholar
  25. 25.
    Ekelund LG, Ekelund C, Roessner S (1982) Antihypertensive effects at rest and during exercise of a calcium blocker, nifedipine, alone and in combination with metoprolol. Acta Med Scand 212: 71–75PubMedCrossRefGoogle Scholar
  26. 26.
    McGregor GA, Rotellar C, Markandu ND, Smith SJ, Sagnella GA (1982) Contrasting effects of nifedipine, captopril and propranolol in normotensive and hypertensive subjects. J Cardiovasc Pharmacol [Suppl 3] 4: S358–S362CrossRefGoogle Scholar
  27. 27.
    Marone C, Luisoli S, Bomio F, Beretta-Piccoli C, Bianchetti MG, Weidmann P (1985) Body sodium-blood volume state, aldosterone, and cardiovascular responsiveness after calcium entry blockade with nifedipine. Kidney Int 28: 658–665PubMedCrossRefGoogle Scholar
  28. 28.
    De Leeuw PW, Smout AJPM, Willemse PJ, Birkenhaeger WH (1981) Effects of verapamil in hypertensive patients. In: Zanchetti A, Krikler D (eds) Proceedings of the international sym-posium on calcium antagonism in cardiovascular therapy. Excerpta Medica, Amsterdam, pp 233–237Google Scholar
  29. 29.
    Leonetti G, Sala C, Bianchini C, Terzoli L, Zanchetti A (1980) Antihypertensive and renal effects of orally administered verapamil. Eur J Clin Pharmacol 18: 375–382PubMedCrossRefGoogle Scholar
  30. 30.
    Schwietzer G, Distler A, Reeck S, Thiede HM, Philipp T (1983) Hypotensive action of calcium antagonists as related to plasma noradrenaline and reactivity to noradrenaline. J Hypertens [Suppl 2] 1: 102–104Google Scholar
  31. 31.
    Spies HF, Koch M, Appel E, Palm D, Kaltenbach MM (1978) EinfluB oraler Langzeittherapie mit Verapamil und Metoprolol auf arteriellen Blutdruck, Herzfrequenz und Plasmakatechol-amine bei Hypertonikern ( Abstr ). Z Kardiol 67: 196Google Scholar
  32. 32.
    Anavekar SN, Christophidis N, Louis WJ, Boyle AE (1981) Verapamil in the treatment of hypertension. J Cardiovasc Pharmacol 3: 287–292PubMedCrossRefGoogle Scholar
  33. 33.
    Hiramatsu K, Yamagishi F, Kubota T, Yamada T (1982) Acute effects of the calcium antagonist nifedipine on blood pressure, pulse rate and the renin-angiotensin-aldosterone system in patients with essential hypertension. Am Heart J 104: 1346–1350PubMedCrossRefGoogle Scholar
  34. 34.
    Guthrie GP Jr, McAllister RG Jr, Kotchen TA (1983) Effects of intravenous and oral verapamil upon pressor and adrenal steroidogenic responses in normal man. J Clin Endocrinol Metab 57: 339–343PubMedCrossRefGoogle Scholar
  35. 35.
    Laederach K, Gerber A, Weidmann P (1984) Effect of calcium antagonist on blood pressure, catecholamines, renin, aldosterone, and cardiovascular pressor responsiveness in normal and hypertensive man. In: Althaus U, Burckhardt D, Vogt E (eds) Proceedings of the international symposium on calcium antagonism. PMI, Frankfurt, pp 93–115Google Scholar
  36. 36.
    Soto ME, Thibonnier M, Sire O, Menard J, Corvol P, Milliez P (1981) Antihypertensive and hormonal effects of single oral dose of captopril and nifedipine in essential hypertension. Eur J Clin Pharmacol 20: 157–161PubMedCrossRefGoogle Scholar
  37. 37.
    Thibonnier M, Bonnet F, Corvol P (1980) Antihypertensive effect of fractionated sublingual administration of nifedipine in moderate essential hypertension. Eur J Clin Pharmacol 17: 161–164PubMedCrossRefGoogle Scholar
  38. 38.
    Bianchetti MG, Beretta-Piccoli C, Weidmann P, Boehringer K, Link L, Morton JJ (1982) Studies on aldosterone responsiveness to angiotensin II during clinical variations in calcium metabolism in normal man. Clin Sci 63: 325–328PubMedGoogle Scholar
  39. 39.
    Nadler JL, Horton R, Hauch V (1984) Therapeutic effect of calcium channel blockade in primary aldosteronism., Clin Res 32: 21AGoogle Scholar
  40. 40.
    Millar JA, McLean K, Reid JL (1981) Calcium antagonists decrease adrenal and vascular responsiveness to angiotensin II in normal man. Clin Sci 61: 65s–68sPubMedGoogle Scholar
  41. 41.
    Weidmann P, Horton R, Maxwell MH, Franklin SS, Fichman M (1973) Dynamic studies of aldosterone in anephric man. Kidney Int 4: 289–298PubMedCrossRefGoogle Scholar
  42. 42.
    Philipp T, Distler A, Cordes U (1978) Sympathetic nervous system and blood pressure control in essential hypertension. Lancet 2: 959–963PubMedCrossRefGoogle Scholar
  43. 43.
    Weidmann P, Keusch G, Flammer J, Ziegler WH, Reubi FC (1979) Increased ratio between changes in blood pressure and plasma norepinephrine in essential hypertension. J Clin Endocrinol Metab 48: 727–731PubMedCrossRefGoogle Scholar
  44. 44.
    Weidmann P, Grimm M, Meier A, Glück Z, Keusch G, Minder I, Beretta-Piccoli C (1980) Pathogenic and therapeutic significance of cardiovascular pressor reactivity as related to plasma catecholamines in borderline and established essential hypertension. Clin Exp Hypertens 2: 427–449PubMedCrossRefGoogle Scholar
  45. 45.
    Bianchetti MG, Weidmann P, Beretta-Piccoli C, Rupp U, Boehringer K, Link L, Ferrier C (1984) Disturbed noradrenergic blood pressure control in normotensive offspring of hypertensive families. Br Heart J 51: 306–311PubMedCrossRefGoogle Scholar
  46. 46.
    Meier A, Weidmann P, Grimm H, Keusch G, Glück Z, Minder I, Ziegler WH (1981) Pressor factors and cardiovascular pressor responsiveness in borderline hypertension. Hypertension 3: 367–372PubMedGoogle Scholar
  47. 47.
    Weidmann P, Beretta-Piccoli C, Keusch G, Glück Z, Mujagic M, Meier A, Ziegler WH (1979) Sodium-volume factor, cardiovascular reactivity and hypotensive mechanisms of diuretic therapy in hypertension associated with diabetes mellitus. Am J Med 67: 779–784PubMedCrossRefGoogle Scholar
  48. 48.
    Beretta-Piccoli C, Weidmann P, Schiffl H, Cottier C, Reubi FC (1982) Enhanced cardiovascular pressor reactivity to norepinephrine in mild renal parenchymal disease. Kidney Int 22: 297–303PubMedCrossRefGoogle Scholar
  49. 49.
    Van Zwieten PA, van Meel JCA, Timmermanns P (1982) Calcium antagonists and alpha-2- adrenoceptors: Possible role of extracellular calcium ions in alpha-2-adrenoceptor-mediated vasoconstriction. J Cardiovasc Pharmacol [Suppl 3] 4: S273–S279CrossRefGoogle Scholar
  50. 50.
    Vanhoutte PM, Timele TJ (1982) Calcium and alpha-adrenoceptors in activation of vascular smooth muscle. J Cardiovasc Pharmacol 4: S280–S286PubMedCrossRefGoogle Scholar
  51. 51.
    Vierhapper H, Waldhausl W (1982) Reduced pressor effect of angiotensin II and of noradrenaline in normal man following the oral administration of the calcium antagonist nifedipine. Eur J Clin Med 12: 263–267Google Scholar
  52. 52.
    Simon G, Snyder DK (1984) Altered pressor responses in long-term nitrendipine treatment. Clin Pharmacol Ther 36: 315–319PubMedCrossRefGoogle Scholar
  53. 53.
    Trost BN, Weidmann P (1984) Hypertension accompanying diabetes mellitus: Antihypertensive and metabolic effects of calcium antagonism. Proceedings of the IXth International Congress of Nephrology, Los Angeles, June 11–16, p 228AGoogle Scholar
  54. 54.
    Brock TA, Lewis LJ, Smith JB (1982) Angiotensin increases Na+ entry and Na+/K+ pump activity in cultures of smooth muscle from rat aorta. Proc Natl Acad Sci USA 79: 1438–1442PubMedCrossRefGoogle Scholar
  55. 55.
    Maisel AS, Motulsky HJ, Insel PA (1985) Hypotension after quinidine plus verapamil. N Engl J Med 312: 167–170PubMedCrossRefGoogle Scholar
  56. 56.
    Aoki K, Kawaguchi Y, Sato K, Kondo S, Yamamoto M (1982) Clinical and pharmacological properties of calcium antagonists in essential hypertension in humans and spontaneously hypertensive rats. J Cardiovasc Pharmacol [Suppl 3] 4: S298–S302CrossRefGoogle Scholar
  57. 57.
    Aoki K, Sato K, Kondo S, Yamamoto M (1983) Hypotensive effects of diltiazem to normal and essential hypertensives. Eur J Clin Pharmacol 25: 475–480PubMedCrossRefGoogle Scholar
  58. 58.
    Guazzi MD, Polese A, Bartorelli A, Loaldi A, Fiorentini C (1982) Evidence of shared mechanism of vasoconstriction in pulmonary and systemic circulation in hypertension: a possible role of intracellular calcium. Circulation 66: 881–886PubMedCrossRefGoogle Scholar
  59. 59.
    Bonaduce D, Ferrara N, Petretta M, Romano E, Postiglione M, Rengo F, Condorelli M (1983) Hemodynamic study of nifedipine administration in hypertensive patients. Am Heart J 105: 865–867PubMedCrossRefGoogle Scholar
  60. 60.
    Lund-Johansen P, Omvik P (1983) Hemodynamic effects of nifedipine in essential hypertension at rest and during exercise. J Hypertens 1: 159–163PubMedCrossRefGoogle Scholar
  61. 61.
    Fouad FM, Pedrinelli R, Bravo EL, Abi-Samra F, Textor SC, Tarazi RC (1984) Clinical and systemic hemodynamic effects of nitrendipine. Clin Pharmacol Ther 35: 768–775PubMedCrossRefGoogle Scholar
  62. 62.
    Kishi Y, Okumura F, Furuya A (1984) Hemodynamic effects of nicardipine hydrochloride. Br J Anaesth 56: 1003–1007PubMedCrossRefGoogle Scholar
  63. 63.
    Garay RP, Dagher G, Pernollet MG, Devynck MA, Meyer P (1980) Inherited defect in Na+, K+-co-transport system in erythrocytes from essential hypertensive patients. Nature 284: 281–283PubMedCrossRefGoogle Scholar
  64. 64.
    Dorst KG, Zidek W, Losse H, Zumkley H, Wollnik S, Vetter H (1981) Intrazellulares Natrium und Calcium als genetische Marker der essentiellen Hypertonic. Schweiz Med Wochenschr 111: 1964–1966PubMedGoogle Scholar
  65. 65.
    Robinson BF (1984) Altered calcium handling as a cause of primary hypertension. J Hypertens 2: 453–460PubMedCrossRefGoogle Scholar
  66. 66.
    Blaustein MP (1977) Sodium ions, calcium ions, blood pressure and hypertension: a reassessment and hypothesis. Am J Physiol 232: C615–C173Google Scholar
  67. 67.
    Hulthen UL, Bolli P, Amann FW, Kiowski W, Biihler FR (1982) Enhanced vasodilatation in essential hypertension by calcium channel blockade with verapamil. Hypertension [Suppl 2] 4: 11-26–11-31Google Scholar
  68. 68.
    Robinson BF, Dobbs RJ, Bailey S (1982) Response of forearm resistance vessels to verapamil and sodium-nitroprusside in normotensive and hypertensive men: evidence for a functional abnormality of vascular smooth muscle in primary hypertension. Clin Sci 63: 33–42PubMedGoogle Scholar
  69. 69.
    Erne P, Bolli P, Burgisse E, Bühler FR (1984) Correlation of platelet calcium with blood pres-sure: effect of antihypertensive therapy. N Engl J Med 310: 1084–1088PubMedCrossRefGoogle Scholar
  70. 70.
    Beretta-Piccoli C, Weidmann P, de Chatel R, Hirsch D, Reubi FC (1977) Beziehungen zwischen Blutdruck, Blutvolumen und Plasmarenin wahrend Diuretikatherapie bei essentieller Hypertonic. Schweiz Med Wochenschr 107: 104–115PubMedGoogle Scholar
  71. 71.
    Flammer J, Weidmann P, Glück Z, Ziegler WH, Reubi FC (1979) Cardiovascular and endocrine profile of adrenergic neurone blockade in normal and hypertensive man. Am J Med 66: 34–42PubMedCrossRefGoogle Scholar
  72. 72.
    Weidmann P, Bousquet JC, Swiss Practitioners Bopindolol Study Group (1986) Antihyperten-sive treatment with bopindolol alone or combined with a diuretic in general practice. J Cardiovasc PharmacolGoogle Scholar
  73. 73.
    Beer N, Gallegos I, Cohen A, Klein N, Sonnenblick E, Frishman W (1981) Efficacy of sub-lingual nifedipine in the acute treatment of systemic hypertension. Chest 79: 571–574PubMedCrossRefGoogle Scholar
  74. 74.
    Palau LG, Minambres FB (1984) Modificaciones ecocardiograficas y de la tension arteral tras la administracion aguda y prolongada (tres meses) de nifedipina. Med Clin (Bare) 83: 146–150Google Scholar
  75. 75.
    Pedersen OL, Christensen CK, Mikkelsen E, Ramsch KD (1980) Relationship between the antihypertensive effect and steady state plasma concentration of nifedipine given alone or in combination with a beta adrenoceptor blocking agent. Eur J Clin Pharmacol 18: 287–293CrossRefGoogle Scholar
  76. 76.
    Chia BL, Ee B, Tan A, Choo M (1982) The immediate hypotensive effect of oral nifedipine. Curr Med Res Opin 8: 139–141PubMedCrossRefGoogle Scholar
  77. 77.
    Bertel O, Conen D, Radü EW, Müller J, Lang C, Dubach UC (1983) Nifedipine in hypertensive emergencies. Br Med J 286: 19–21CrossRefGoogle Scholar
  78. 78.
    Conen D, Bertel O, Dubach UC (1982) An oral calcium antagonist for the treatment of hypertensive emergencies. J Cardiovasc Pharmacol 4: S378–S382PubMedCrossRefGoogle Scholar
  79. 79.
    Aoki K, Kondo S, Mochizuki A, Yoshida T, Kato S, Kato K, Takikawa K (1978) Antihypertensive effect of cardiovascular Ca2+-antagonist in hypertensive patients in the absence and presence of beta-adrenergic blockade. Am Heart J 96: 218–226PubMedCrossRefGoogle Scholar
  80. 80.
    Degenhardt S, Hummerich W, Lang R (1984) Akute hamodynamische und hormonelle Effekte einer sublingualen Einmaldosis von Nifedipin bei Hypertonikern. Nieren Hochdruckkr 13: 494–499Google Scholar
  81. 81.
    Guazzi MD, de Cesare N, Galli C, Salvioni A, Tramontana C, Tamborini G, Bartorelli A (1984) Calcium-channel blockade with nifedipine and angiotensin converting-enzyme inhibiton with captopril in the therapy of patients with severe primary hypertension. Circulation 70: 279–284Google Scholar
  82. 82.
    Aoki K, Kondo S, Sato K, Kato K, Kawaguchi Y, Mochizuki A, Yamamoto M (1981) Hypotensive action of nifedipine ( Ca-antagonist) and propranolol in acute trials and its long-term therapy of hypertensive coronary heart disease patients. Jpn Heart J 22: 575–584Google Scholar
  83. 83.
    De Divitiis O, Petitto M, di Somma S, Fazio M, Galderisi M, Villari B, Liguori V, Santomauro M (1984) Acebutolol and nifedipine in the treatment of arterial hypertension: efficacy and acceptability. Drug Res 34(l)/6: 710–715Google Scholar
  84. 84.
    Levenson JA, Safar ME, Simon AC, Boutier JA, Griener L (1983) Systemic and arterial hemo-dynamic effects of nifedipine (20 mg) in mild-to-moderate hypertension. Hypertension [Suppl 5] 5: V-57–V-60Google Scholar
  85. 85.
    Maeda K, Tanaka C, Minamikawa H, Komatsu H, Kotsumi K, Inoue E (1982) Antihypertensive effects of the calcium antagonistic agent nifedipine. Drug Res 32 (1): 267–271Google Scholar
  86. 86.
    Imai Y, Abe K, Otsuka Y, Irokawa N, Yasujima M, Saito K, Sakurai Y, Chiba S, Ito T, Sato M, Haruyama T, Miura Y, Yoshinaga K (1980) Management of severe hypertension with nifedipine in combination with clonidine or propranolol. Drug Res 30(1): 674–67Google Scholar
  87. 87.
    Masotti G, Poggesi L, Castellani S, Moretti A, Galanti G, Scarti L (1984) A study of the anti-hypertensive effect and some pharmacodynamic aspects of nifedipine in medium-term treatment. Int J Clin Pharmacol Res 4 (1): 71–79PubMedGoogle Scholar
  88. 88.
    Stornello M, di Rao G, Iachello M, Pisani R, Scapellato L, Pedrinelli R, Salvetti A (1983) Hemodynamic and humoral interactions between captopril and nifedipine. Hypertension [Suppl 3] 5: III-154–III-156Google Scholar
  89. 89.
    Pedersen OL, Mikkelsen E, Andersson KE (1978) Effects of extracellular calcium on potassium and noradrenaline induced contractions in the aorta of spontaneously hypertensive rats-increased sensitivity to nifedipine. Acta Pharmacol Toxicol (Copenh) 43: 137–144CrossRefGoogle Scholar
  90. 90.
    Douglas-Jones AP, Mitchell AD (1984) Comparison of nifedipine (retard formulation) and mefruside in the treatment of mild to moderate hypertension — a prospective randomized double-blind crossover study in general practice. Postgrad Med J 60: 529–532PubMedCrossRefGoogle Scholar
  91. 91.
    Klein W, Brandt D, Vrecko K, Haerringer M (1983) Role of calcium antagonists in the treatment of essential hypertension. Circ Res [Suppl 1] 52: 174–181Google Scholar
  92. 92.
    Erne P, Bolli P, Bertel O, Hulthen UL, Kiowski W, Müller FB, Bühler FR (1983) Factors influencing the hypotensive effects of calcium antagonists. Hypertension [Suppl 2] 5:11-97–11-102Google Scholar
  93. 93.
    Valdes G, Montero J, Tobar M, Chacon C, Croxatto HR (1983) Effecto initial y cronico de nifedipina en pacientes hypertensos. Rev Med Chil 111: 1237–1240PubMedGoogle Scholar
  94. 94.
    Hallin L, Andren L, Hansson L (1983) Controlled trial of nifedipine and bendroflumethiazide in hypertension. J Cardiovasc Pharmacol 6: 1083–1085CrossRefGoogle Scholar
  95. 95.
    Lewis GRJ (1980) Verapamil in the management of chronic hypertension. Clin Invest Med 3: 175–177PubMedGoogle Scholar
  96. 96.
    Loaldi A, Pepi M, Agostini PG, Fiorentini C. Gracio S, della Bella P, Guazzi MD (1983) Cardiac rhythm in hypertension assessed through 24 hour ambulatory electrocardiographic monitoring: effects of load manipulation with atenolol, verapamil and nifedipine. Br Heart J 50: 118–126PubMedCrossRefGoogle Scholar
  97. 97.
    Terzoli L, Bianchini C, Sala C, Sernesi L, Leonetti G, Zanchetti A (1978) Effetto sulla pressione arteriosa e sul bilancio indrosalino della somministrazione cronica del verapamil in pazienti ipertesi. Boll Soc Ital Cardiol 13 (10): 1773–1778Google Scholar
  98. 98.
    De Leeuw PW, Birkenhager WH (1984) Effects of verapamil in hypertensive patients. Acta Med Scand [Supp l] 681: 125–128Google Scholar
  99. 99.
    Mitbo K, Hals O (1980) Verapamil in the treatment of hypertension. Curr Ther Res 27: 830–837Google Scholar
  100. 100.
    Anavekar SN, Christophidis N, Louis WJ, Doyle AE (1981) Verapamil in the treatment of hypertension. J Cardiovasc Pharmacol 3: 287–292PubMedCrossRefGoogle Scholar
  101. 101.
    Doyle AE (1983) Comparison of beta-adrenoceptor blockers and calcium antagonists in hypertension., Hypertension [Suppl 2] 5: II-103–II-108Google Scholar
  102. 102.
    Mitbo K, Hals O, van der Meer J (1982) Verapamil compared with nifedipine in the treatment of essential hypertension. J Cardiovasc Pharmacol 4: S363–S368CrossRefGoogle Scholar
  103. 103.
    Hornung RS, Jones RI, Gould BA, Sonecha T, Raftery EB (1984) Propranolol vs verapamil for the treatment of essential hypertension. Am Heart J 108: 554–560PubMedCrossRefGoogle Scholar
  104. 104.
    Gould BA, Mann S, Kieso H, Subramanian VB, Raftery EB (1981) The 24-h intraarterial ambulatory profile of blood pressure reduction with verapamil. In: Zanchetti A, Krikler DM (eds) International Symposium, Florence. Excerpta Medica, Amsterdam, pp 280–291Google Scholar
  105. 105.
    Bühler FR, Hulthen UL, Kiowski W, Bolli P (1982) Greater antihypertensive efficacy of the calcium channel inhibitor verapamil in older and low renin patients. Clin Sci 63: s439–s441Google Scholar
  106. 106.
    Lund-Johansen P (1984) Hemodynamic effects of verapamil in essential hypertension at rest and during exercise. Acta Med Scand [Supp l] 681: 109–115CrossRefGoogle Scholar
  107. 107.
    Wigler I, Peer G, Sofermann G, Blum M, Aviram A (1984) Long-term treatment of arterial hypertension with verapamil. Int J Clin Pharmacol Ther Toxicol 22: 162–166PubMedGoogle Scholar
  108. 108.
    Lopez LM, Metha JL, Baz R, Aguila E (1984) Effects of nitrendipine and hydralazine on plasma catecholamines in essential hypertension. Clin Pharm 36 (4): 444–450Google Scholar
  109. 109.
    Kazda S, Garthoff B, Ramsch KD, Schlüter G (1983) Nisoldipine. In: Scriabine A (ed) New drugs annual: Cardiovascular drugs. Raven, New York, pp 243–258Google Scholar
  110. 110.
    Wambach G, Breuer G, Kaufmann W (1984) Hypotensive Eigenschaften von Nisoldipin. Drug Res 34 (1): 620–623Google Scholar
  111. 111.
    Leonetti G, Gradnik R, Terzoli L, Fruscio M, Rupoli L, Zanchetti A (1984) Felodipine, a new vasodilating drug: blood pressure, cardiac, renal, and humoral effects in hypertensive patients. J Cardiovasc Pharmacol 6: 392–398PubMedCrossRefGoogle Scholar
  112. 112.
    Andersson O, Bengtsson C, Elmfeldt D, Haglund K, Hedner T, Seideman P, Sjoberg KH, Stromgren E, Aberg H, Oestman J (1984) Short-term effects of felodipine, a new dihydro-pyridine in hypertension. Br J Clin Pharmacol 17: 257–263PubMedGoogle Scholar
  113. 113.
    Rosatti F, Cella PL, Fici F, Rossi F, Chieppa S, Marmo E (1984) Diltiazem in the therapy of arterial hypertension: Polygraphic assessment of left ventricular performance. Curr Ther Res 36: 701–711Google Scholar
  114. 114.
    Yamakado T, Oonishi N, Kondo S, Noziri A, Nakano T, Takezawa H (1983) Effects of diltiazem on cardiovascular responses during exercise in systemic hypertension and comparison with propranolol. Am J Cardiol 52: 1023–1027PubMedCrossRefGoogle Scholar
  115. 115.
    Inouye IK, Massie BK, Benowitz N, Simpson PM, Loge D (1984) Antihypertensive therapy with diltiazem and comparison with hydrochlorothiazide. Am J Cardiol 53: 1588–1592PubMedCrossRefGoogle Scholar
  116. 116.
    Trimarco B, de Lucia N, Ricciardelli B, Volpe M, Veniero A, Cuocolo A, Cicala M (1984) Diltiazem in the treatment of mild to moderate essential hypertension. Comparison with metoprolol in a crossover double-blind trial. J Clin Pharmacol 24: 218–227PubMedGoogle Scholar
  117. 117.
    Gerold M, Eigenmann R, Haeusler G (1982) Cardiovascular effects of tiapamil (Ro 11-1781), a new calcium entry blocker. J Cardiovasc Pharmacol 4: 419–429PubMedCrossRefGoogle Scholar
  118. 118.
    Laederach K, Weidmann P, Lauener F, Gerber A, Ziegler WH (1986) Comparative acute effects of the calcium channel blockers tiapamil, nisoldipine and nifedipine on blood pressure and some regulatory factors in normal and hypertensive subjects. J Cardiovasc Pharmacol (in press)Google Scholar
  119. 119.
    Ventura HO, Messerli FH, Oigman W, Dunn FG, Reisin E, Fröhlich ED (1983) Immediate hemodynamic effects of a new calcium channel blocking agent (nitrendipine) in essential hyper-tension. Am J Cardiol 51: 783–786PubMedCrossRefGoogle Scholar
  120. 120.
    Van Schaik BAM, Vanniste AE, Geyskess GG (1984) Antihypertensive and renal effects of nicardipine. Br J Clin Pharmacol 18: 57–63PubMedGoogle Scholar
  121. 121.
    Klütsch K, Schmidt P, Grosswendt J (1982) Der Einfluß von „Bay a 1040” auf die Nierenfunk- tion des Hypertonikers. Drug Res 22: 377–380Google Scholar
  122. 122.
    Yokoyama S, Kaburagi T (1983) Clinical effects of intravenous nifedipine on renal function. J Cardiovasc Pharmacol 5: 67–71PubMedCrossRefGoogle Scholar
  123. 123.
    Thananopavara C, Golub MS, Eggena P, Barret JD, Sambhi MP (1984) Renal effects of nitrendipine monotherapy in essential hypertension. J Cardiovasc Pharmacol 6: S1032–S1036CrossRefGoogle Scholar
  124. 124.
    Husted SE, Nielsen HK, Christensen CK, Pedersen OL (1982) Long-term therapy of arterial hypertension with nifedipine given alone or in combination with a beta-adrenoceptor blocking agent. Eur J Clin Pharmacol 22: 101–103PubMedCrossRefGoogle Scholar
  125. 125.
    Zawar PB, Chawhan RN, Gosavi SV, Gokhale PD, Jadhav AB (1982) Verapamil in hypertension-a long-term study. Indian Heart J 34: 38–41PubMedGoogle Scholar
  126. 126.
    Taburet AM, Singlas E, Colin JN, Banzet O, Thibonnier M, Corvol P (1983) Pharmacokinetic studies of nifedipine tablet. Correlation of antihypertensive effects. Hypertension 5(2): II-29–II-33Google Scholar
  127. 127.
    Taylor SH, Silke B, Ahuya C, Okoli R (1982) Influence of nicardipine on the blood pressure at rest and on the pressor responses to cold, isometric exertion and dynamic exercise in hypertensive patients. J Cardiovasc Pharmacol 4: 803–807PubMedCrossRefGoogle Scholar
  128. 128.
    Magometschnigg D (1983) Acute hypotensive response to nifedipine. Hypertension [Suppl 2] 5.11-80–11-84Google Scholar
  129. 129.
    Yoshimura M, Takashina R, Shikuma R, Takahashi H, Takeda K, Ashizawa H, Ochi Y, Ijchi H (1983) Antihypertensive effect of nifedipine and its relationship to severity of hypertension. Drug Res 3: 254–257Google Scholar
  130. 130.
    Maeda K, Takasugi T, Tsukano Y, Tanaka Y, Shiota K (1981) Clinical study on the hypotensive effects of diltiazem hydrochloride. Int J Clin Pharmacol Ther Toxicol 19: 47–55PubMedGoogle Scholar
  131. 131.
    Orö L, Ryman T (1984) Long-term study of the combined antihypertensive action of nitrendipine and metoprolol. In: Scriabin A, Vanov S, Deck K (eds) Nitrendipine. Urban and Schwarzenberg, Munich, pp 527–534Google Scholar
  132. 132.
    Tammen AT, Stoepel K, Vollmer G, Blümchen G (1984) Efficacy and safety in patients with essential hypertension and coronary heart disease. In: Scriabin A, Vanov S, Deck K (eds) Nitrendipine. Urban and Schwarzenberg, Munich, pp 469–476Google Scholar
  133. 133.
    Yagil Y, Kobrin I, Stessmann J, Ghanem J, Leibel B, Ben-Ishay D (1983) Effectiveness of combined nifedipine and propranolol treatment in hypertension. Hypertension [Suppl 2] 5:11-113–11-117Google Scholar
  134. 134.
    Aoki K, Sato K (1982) Acute hypotensive, hemodynamic effects of long-term treatment with niludipine, a Ca2+-antagonist, in patients with essential hypertension. Drug Res 32(2) 9: 1141–1145Google Scholar
  135. 135.
    Eggertsen R, Hansson L (1982) Effects of treatment with nifedipine and metoprolol in essential hypertension. Eur J Clin Pharmacol 21: 389 - 390PubMedCrossRefGoogle Scholar
  136. 136.
    Brennan FN, Blake S (1982) The use of nifedipine as a third-step agent in the treatment of refractory hypertension. Ir Med J 75: 29 - 30PubMedGoogle Scholar
  137. 137.
    Dean S, Kendall MJ (1983) Nifedipine in treatment of difficult hypertensives. Eur J Clin Pharmacol 24: 1 - 5PubMedCrossRefGoogle Scholar
  138. 138.
    Murphy MB, Scriven AJI, Dollery CT (1983) Efficacy of nifedipine as a step 3 antihypertensive drug. Hypertension [Suppl 2] 5:II-118–II-121Google Scholar
  139. 139.
    Gonzalez-Gomez A, Gamio-Capestany F, Garcia-Barreto D (1983) Hypotensive action of verapamil in a group of hydralazine-dependent hypertensive patients. Arch Intern Med 261: 268–277Google Scholar
  140. 140.
    Leary WP, Asmal AC (1979) Treatment of hypertension with verapamil. Curr Ther Res 25: 747–751Google Scholar
  141. 141.
    Ueda K, Musakami M (1983) A controlled comparative multicenter study on the clinical efficacy of nifedipine in the treatment of severe hypertension. In: Kaltenbach M, Neufeld HN (eds) 5th International Adalat Symposium. Excerpta Medica, Amsterdam, p 146Google Scholar
  142. 142.
    Guazzi MD, Fiorentini C, Olivari MT, Bartorelli A, Necchi G, Polese A (1980) Short- and long-term efficacy of a calcium-antagonistic agent (nifedipine) combined with methyldopa in the treatment of severe hypertension. Circulation 61: 913–919PubMedGoogle Scholar
  143. 143.
    Jee LD, Opie LH (1983) Acute hypotensive response to nifedipine added to prazosin in treatment of hypertension (case reports). Br Med J 287: 1514CrossRefGoogle Scholar
  144. 144.
    Kusano E, Asano Y, Takeda K, Matsumoto Y, Ebihara A, Hosoda S (1982) Hypotensive effect of nifedipine in hypertensive patients with chronic renal failure. Drug Res 32: 1575–1580Google Scholar
  145. 145.
    Kubo K, Shiraishi K, Muto H, Suzuki T, Sugino N (1983) Treatment of hypertension in hemodialysis patients with nifedipine. Hypertension [Suppl 2] 5: II-109–II-112Google Scholar
  146. 146.
    Yamakado M, Tagawa T (1978) Hypotensive effects of diltiazem HC1 ( Herbesser ). Mod Clin Med 20: 1877–1881Google Scholar
  147. 147.
    Sakurai T, Kurita T, Nagano S, Sonoda T (1972) Antihypertensive vasodilating and sodium diuretic actions of D-cis-isomer of benzothiazepine derivate (CRD-401). Acta Urolog Jpn 18: 695Google Scholar
  148. 148.
    Trost BN, Weidmann P (1984) Effects of nitrendipine and other calcium antagonists on glucose metabolism in man. J Cardiovasc Pharmacol 6: S986–S995PubMedCrossRefGoogle Scholar
  149. 149.
    Donelly T, Harrower ADP (1980) Effect of nifedipine on glucose tolerance and insulin secretion in diabetic and non-diabetic patients. Curr Med Res Opin 6: 690–693CrossRefGoogle Scholar
  150. 150.
    Abadie E, Passa PH (1984) Diabetogenic effects of nifedipine ( Letter ). Br Med J 289: 438Google Scholar
  151. 151.
    Bhatnagar SK, Amin MAA, Al-Yusuf AR (1984) Diabetogenic effects of nifedipine. Br Med J 289: 19CrossRefGoogle Scholar
  152. 152.
    Guazzi MD, Olivari MT, Polese A, Fiorentini C, Magrini F, Moruzzi P (1977) Nifedipine, a new antihypertensive with rapid action. Clin Pharmacol Ther 22: 528–532PubMedGoogle Scholar
  153. 153.
    Bartorelli C, Magrini F, Moruzzi P, Olivari MT, Polese A, Fiorentini C, Guazzi MD (1978) Hemodynamic effect of a calcium-antagonistic agent (nifedipine) in hypertension: therapeutic implications. Clin Sci Mol Med 55: 291s–292sGoogle Scholar
  154. 154.
    Kuwajima I, Ueda K, Kamata C, Matsushita S, Kuramoto K, Murakami H, Hada Y (1978) A study on the effects of nifedipine in hypertensive crises and severe hypertension. Jpn Heart J 19: 455–467PubMedCrossRefGoogle Scholar
  155. 155.
    Huysmans FTM, Sluiter HE, Thien TA, Koene RAP (1983) Acute treatment of hypertensive crisis with nifedipine. Br J Clin Pharmacol 16: 725–727PubMedGoogle Scholar
  156. 156.
    Magometschnigg D (1982) Zur Therapie bei hypertonen Krisen. Nifedipin per os. Dtsch Med Wochenschr 107: 1423–1428PubMedCrossRefGoogle Scholar
  157. 157.
    Anonymous (1983) Calcium antagonists and aneurysmal subarachnoid hemorrhage. Lancet I: 141–143Google Scholar
  158. 158.
    Nobile-Orazio E, Sterzi R (1981) Cerebral ischemia after nifedipine treatment. Br Med J 283: 948CrossRefGoogle Scholar
  159. 159.
    Polese A, Fiorentini C, Olivari MT, Guazzi MD (1979) Clinical use of a calcium antagonistic agent (nifedipine) in acute pulmonary edema. Am J Med 66: 825–830PubMedCrossRefGoogle Scholar
  160. 160.
    Bhat RP, Wasir HS (1982) Verapamil infusion in hypertension. Indian Heart J 34: 228–231PubMedGoogle Scholar
  161. 161.
    Rosenthal J (1981) Die Behandlung der hypertensiven Krisen mit Diltiazem. In: Bender F, Greeff K (eds) 1. Diltiazem-Symposium. Excerpta Medica, Amsterdam, pp 227–248Google Scholar
  162. 162.
    Krebs R (1983) Adverse reactions with calcium antagonists. Hypertension [Suppl 2] 5: II-125–II-129Google Scholar
  163. 163.
    Eisenberg JNH, Oakley GDG (1984) Probable adverse interaction between oral metoprolol and verapamil. Postgrad Med 60: 705–706CrossRefGoogle Scholar
  164. 164.
    Hutchinson SJ, Lorimer AR (1984) Betablockers and verapamil: a cautionary tale. Br Med J 289: 659–660CrossRefGoogle Scholar
  165. 165.
    Ramon Y, Behar S, Kishon Y, Engelberg IS (1984) Gingival hyperplasia caused by nifedipine - a preliminary report. Int J Cardiol 5: 195–204PubMedCrossRefGoogle Scholar
  166. 166.
    Diamond JR, Cheung JY, Fang LST (1984) Nifedipine-induced renal dysfunction. Am J Med 77: 905–909PubMedCrossRefGoogle Scholar
  167. 167.
    Ter Wee PM, Rosman JB, van der Geest S (1984) Acute renal failure due to diltiazem. Lancet 11: 1337–1338CrossRefGoogle Scholar
  168. 168.
    Murphy MB, Scriven AJI, Dollery CT (1983) Role of nifedipine in treatment of hypertension. Br Med J 287: 257–259CrossRefGoogle Scholar
  169. 169.
    Giesecke HJ, Guckenbiehl W, Hagemann I (1982) Ergebnisse einer Multicenterstudie mit Diltiazem bei Hypertonic., In: Bender F, Greeff K (eds) 1. Diltiazem-Symposium. Excerpta Medica, Amsterdam, pp 220–226Google Scholar
  170. 170.
    Schulte KL, Meyer WA, Distler A, Gotzen R (1983) Antihypertensive Langzeitbehandlung mit Diltiazem und Nifedipin bei essentieller Hypertonic. Therapiewoche 33: 6011–6014Google Scholar
  171. 171.
    Röjdmark S, Andersson DEH (1984) Influence of verapamil on glucose tolerance. Acta Med Scand [Suppl] 681: 37–48Google Scholar
  172. 172.
    Segrestaa JM, Caulin C, Dahan R, Houlbert D, Thiercelin JF, Herman P, Sauvanet JP, Larribaud J (1984) Effect of diltiazem on plasma glucose, insulin and glucagon during an oral glucose tolerance test in healthy volunteers., Eur J Clin Pharmacol 26: 481–483PubMedCrossRefGoogle Scholar
  173. 173.
    Walldius G (1984) Effect of verapamil on serum lipoproteins in patients with angina pectoris. Acta Med Scand [Suppl] 681: 43–48Google Scholar
  174. 174.
    Weidmann P, Uehlinger DE, Gerber A (1985) Antihypertensive treatment and serum lipo-proteins. J Hypertens 3: 297–306PubMedCrossRefGoogle Scholar
  175. 175.
    Lessem J, Bellinetto A (1983) Interaction between digoxin and the calcium antagonists nicardipine and tiapamil. Clin Ther 5: 595–602PubMedGoogle Scholar
  176. 176.
    Pedersen KE (1984) The influence of calcium antagonists on plasma digoxin concentration. Acta Med Scand [Suppl] 681: 31–36Google Scholar
  177. 177.
    Helgeland A (1980) Treatment of mild hypertension: a five-year controlled drug trial. The Oslo Study. Am J Med 69: 725–732PubMedCrossRefGoogle Scholar
  178. 178.
    Multiple risk factor intervention trial research group (MRFIT) (1982) Risk factor changes and mortality results. JAMA 248: 1465–1477CrossRefGoogle Scholar
  179. 179.
    Morgan TO, Adams WR, Hodgson M, Gibberd RW (1980) Failure of therapy to improve prognosis in elderly males with hypertension. Med J Aust 2: 27–31PubMedGoogle Scholar
  180. 180.
    Evans MG, Olanoff LS, Hurwitz G, Cowart D, Conradi EC (1984) Use of nifedipine as an adjunct to current antihypertensive therapy. Arch Intern Med 144: 985–987PubMedCrossRefGoogle Scholar
  181. 181.
    Murphy MB, Bulpitt CJ, Doliery CT (1984) Role of nifedipine in the treatment of resistant hypertension. Am J Med 77 (2B): 16–21PubMedGoogle Scholar
  182. 182.
    Andren L, Hansson L, Oroe L, Ryman T (1982) Experience with nitrendipine — a new calcium antagonist — in hypertension. J Cardiovasc Pharmacol 4: S387–S391PubMedCrossRefGoogle Scholar
  183. 183.
    Dunn JM, Groth PE (1984) Once daily verapamil. Lancet II: 1338–1339Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1986

Authors and Affiliations

  • P. Weidmann
    • 1
  • M. P. Gnaedinger
    • 1
  • D. E. Uehlinger
    • 1
  1. 1.Medizinische PoliklinikBernSwitzerland

Personalised recommendations