title: Calcium antagonists and vascular smooth muscle cell reactivity.
abstract: OBJECTIVE
  To determine the mechanisms whereby calcium channel blockers (CCBs) control the reactivity of vascular smooth muscle cells (VSMCs).
  
  
  BACKGROUND
  Although CCBs are known to play an important role in the calcium homeostasis of VSMCs, they are suspected to exert additional effects in this cell type. Thus, the possibility that CCBs could affect VSMC growth/proliferation through a mechanism distinct from the inhibition of calcium channels was investigated.
  
  
  METHODS
  VSMCs were isolated from rat aortae and cultured. The influence of nifedipine and amlodipine on basic fibroblast growth factor (bFGF)-stimulated DNA synthesis and proliferation was studied by measuring bFGF-induced BrdU incorporation into VSMCs and cell counts, respectively. The influence of amlodipine (and of isradipine) on the mobilization of intracellular Ca2+ stores was determined by studying the fluorescence of thapsigargin-stimulated VSMCs pre-labeled with the fluoroprobe Fura-2.
  
  
  RESULTS
  Both nifedipine and amlodipine inhibited bFGF-induced VSMC growth/proliferation. In the case of nifedipine but not in that of amlodipine, this inhibitory effect could be accounted for by the L-type Ca(2+)-channel antagonist property of the drug. On the other hand, amlodipine but not isradipine, diltiazem, and verapamil, did inhibit thapsigargin-induced Ca2+ mobilization.
  
  
  CONCLUSIONS
  These findings suggest that in addition to its L-type Ca(2+)-channel antagonist property, amlodipine also exerts a "thapsigargin-like" activity which, together with its particular antioxidant property, might participate in its antiatherogenic potency.
authors.affiliation: CNRS UMR 8604 Faculté de Médecine Necker, Paris, France. marche@necker.fr
authors.forename: P
authors.initials: P
authors.lastname: Marche
authors.forename: O
authors.initials: O
authors.lastname: Stepien
mesh_terms: D017311:Amlodipine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D013329:Structure-Activity Relationship
chemical_list: D002121:Calcium Channel Blockers; D017311:Amlodipine; D009543:Nifedipine; D002118:Calcium