title: 1α,25-dihydroxycholecalciferol induces nitric oxide production in cultured endothelial cells.
abstract: BACKGROUND
  Recently, 1α,25-dihydroxycholecalciferol (vitD) has received increasing interest for its effects on many tissues and organs other than bone. A number of experimental studies have shown that vitD may have an important role in modifying risk for cardiovascular disease.
  
  
  OBJECTIVE
  This study was planned to test the effects of vitD on endothelial nitric oxide (NO) production and to study the intracellular pathways leading to NO release.
  
  
  METHODS
  In human umbilical vein endothelial cells (HUVEC) cultures the effects of vitD on NO production and p38, Akt, ERK and eNOS phosphorylations were examined in absence or in presence of the NO synthase inhibitor L-NAME and protein kinases specific inhibitors SB203580, wortmannin and UO126.
  
  
  RESULTS
  VitD caused a concentration-dependent increase in NO production. The maximum effect was observed at a concentration of 1 nM and the optimal time of stimulation was 1 min. Effects induced by vitD were abolished by L-NAME and by pre-treatment with protein kinases inhibitors. To verify the effective involvement of vitD receptor (VDR) in the action mechanism of vitD, experiments were repeated in presence of the specific VDR ligands ZK159222 and ZK191784.
  
  
  CONCLUSIONS
  The results of this study demonstrate that vitD can induce a significant increase in endothelial NO production. VitD interaction with VDR caused the phosphorylation of p38, AKT and ERK leading to eNOS activation.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Eastern Piedmont, Novara, Italy. molinari@med.unipmn.it
authors.forename: Claudio
authors.initials: C
authors.lastname: Molinari
authors.forename: Francesca
authors.initials: F
authors.lastname: Uberti
authors.forename: Elena
authors.initials: E
authors.lastname: Grossini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vacca
authors.forename: Stefano
authors.initials: S
authors.lastname: Carda
authors.forename: Marco
authors.initials: M
authors.lastname: Invernizzi
authors.forename: Carlo
authors.initials: C
authors.lastname: Cisari
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D004100:Dihydroxycholecalciferols / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis*
chemical_list: D004100:Dihydroxycholecalciferols; D009569:Nitric Oxide