[Molecular effects of new calcium antagonists: is the principle of parcimony out of place?].
The calcium (Ca2+) channel antagonists (CCA) are used successfully in the treatment of hypertension and angina pectoris. Their mode of action is to decrease Ca2+ entry in the vascular smooth muscle cells. Their molecular targets are voltage activated Ca2+ channels (VACC), especially the L-type (VACC-L). This review examines the role of the VACC-L and of the T-type (VACC-T) in vascular physiology and hypertension. The molecular mechanisms at the base of the vascular selectivity of CCA are presented with, in filigree, the concern of trying to understand the effect of recently developed molecules. In particular, we will examine the ideas having recently emerged concerning the mode of action of last generation dihydropyridines (DHPs) stripped of some of the undesirable effects of prototypes AC considered as highly specific of the VACC-L. These properties could result, in particular, from their effects on the VACC-T, which could occur in addition to those classically observed on the VACC-L.
Richard
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Inserm U637, physiopathologie cardiovasculaire, CHU Arnaud-de-Villeneuve, 371, avenue du Doyen-Faston-Giraud, 34295 Montpellier cedex 5, France. sylvain.richard@inserm.fr
Virsolvy
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Fort
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D032761:Animal Experimentation; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use*; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020747:Calcium Channels, T-Type / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D004095:Dihydropyridines / Q000494:pharmacology; D004594:Electrophysiology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D006977:Hypertension, Renal / Q000188:drug therapy; D007678:Kidney Glomerulus; D051379:Mice; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D014661:Vasoconstriction / Q000502:physiology
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D004095:Dihydropyridines