Calcium Entry Blockers in Cardiovascular and Cerebral Dysfunctions

1. Front Matter

   Pages i-vii

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2. Introductory considerations

   1. Front Matter

      Pages 1-1

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   2. The major steps in the discovery of calcium entry blockers

      • A. G. Herman

      Pages 3-7

   3. Basic mechanisms and classification of calcium entry blockers

      • T. Godfraind

      Pages 9-18

   4. Calcium entry blockers: Perspectives

      • A. Schwartz

      Pages 19-23

   5. Twenty-seven calcium entry blockers in development: a new chapter in pharmacology

      • D. Wellens

      Pages 25-42

3. Calcium entry blockers and peripheral circulatory function

   1. Front Matter

      Pages 43-43

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   2. Calcium-ions and excitation contraction coupling in vascular smooth muscle cells

      • R. Casteels

      Pages 45-52

   3. Laser microprobe mass analysis (LAMMA) as a technique to quantitate Ca2+ ions

      • S. De Nollin, W. Jacob, R. Hertsens

      Pages 53-58

   4. Vascular pharmacology of calcium entry blockers

      • J. M. Van Nueten

      Pages 59-72

   5. Calcium homeostasis in human red blood cells

      • H.J. Schatzmann

      Pages 73-79

   6. Impact of Ca2+ entry blockers on Ca2+-dependent mechanisms in red blood cells, platelets and endothelial cells

      • F. De Clerck, J. Hladovec

      Pages 81-90

   7. Red blood cell microrheology and calcium antagonists

      • J. F. Stoltz

      Pages 91-102

   8. Calcium entry blockers in the treatment of peripheral obliterative arterial disease

      • T. Di Perri, F. Laghi Pasini, M. Guerrini

      Pages 103-110

4. Calcium entry blockers and myocardial function

   1. Front Matter

      Pages 111-111

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   2. Pharmacology of calcium entry blockers in animal and human coronary arteries

      • T. Godfraind, R. C. Miller

      Pages 113-124

   3. Calcium paradox and calcium entry blockers

      • T. J. C. Ruigrok, M. A. Slade, W. G. Nayler, F. L. Meijler

      Pages 125-134

   4. Myocardial oxygen deprivation and calcium deprivation: ultrastructural characteristics and clinical significance

      • G. R. Bullock, D. J. Hearse

      Pages 135-143

   5. Basic and clinical aspects of myocardial protection by calcium entry blockers

      • M. Borgers, W. Flameng

      Pages 145-153

   6. Effect of calcium entry blockers on impaired left ventricular wall motion

      • P. F. Cohn

      Pages 155-160

2 The free internal Ca+ concentration in human red cells is set according to the leak­ 2 and-pump principle: There is a finite passive Ca+ influx at the physiological 2 2 Ca+ -gradient across the membrane which is compensated by Ca+ pumping in the outward direction with a rate given by the degree of saturation of the A TP-fuelled Ca­ 2 pump at the steady-state internal Ca+ concentration. Simons (1982) recently devised a method allowing the measurement of the steady­ 2 2 state internal Ca+ concentration. Cells are suspended in media of different Ca+ con­ 2 2 tent whose Ca+ concentration is monitored by a Ca+ -selective electrode. When the cells are lysed (by digitonin) there is an upward or downward deflection of the elec­ 2 trode signal. At the point of zero deflection, the cellular Ca+ concentration equals that 2 of the medium. The result is, that in fresh human red blood cells the Ca+ concentra­ tion is ;;;; O.4,uM (this is an upper estimate; the true value may be considerably lower).

• angina pectoris
• arterial pressure
• cardiovascular
• hemodynamics
• hypertension

• Laboratoire de Pharmacodynamie Générale et de Pharmacologie, Université Catholique de Louvain, Brussels, Belgium

  Théophile Godfraind

• Department of Medicine, University of Antwerp, Wilrijk, Belgium

  Arnold G. Herman

• Janssen Pharmaceutica, Beerse, Belgium

  Donald Wellens

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