title: Hydrogen peroxide activates store-operated Ca(2+) entry in coronary arteries.
abstract: OBJECTIVE
  Abnormal Ca(2+) metabolism has been involved in the pathogenesis of vascular dysfunction associated with oxidative stress. Here, we have investigated the actions of H2 O2 on store-operated Ca(2+) (SOC) entry in coronary arteries and assessed whether it is impaired in arteries from a rat model of metabolic syndrome.
  
  
  METHODS
  Simultaneous measurements of intracellular Ca(2+) concentration and contractile responses were made in coronary arteries from Wistar and obese Zucker rats, mounted in microvascular myographs, and the effects of H2 O2 were assessed.
  
  
  RESULTS
  H2 O2 raised intracellular Ca(2+) concentrations, accompanied by simultaneous vasoconstriction that was markedly reduced in a Ca(2+) -free medium. Upon Ca(2+) re-addition, a nifedipine-resistant sustained Ca(2+) entry, not coupled to contraction, was obtained in endothelium-denuded coronary arteries. The effect of H2 O2 on this voltage-independent Ca(2+) influx was concentration-dependent, and high micromolar H2 O2 concentrations were inhibitory and reduced SOC entry evoked by inhibition of the sarcoplasmic reticulum ATPase (SERCA). H2 O2 -induced increases in Fura signals were mimicked by Ba(2+) and reduced by heparin, Gd(3+) ions and by Pyr6, a selective inhibitor of the Orai1-mediated Ca(2+) entry,. In coronary arteries from obese Zucker rats, intracellular Ca(2+) mobilization and SOC entry activated by acute exposure to H2 O2 were augmented and associated with local oxidative stress.
  
  
  CONCLUSIONS
  H2 O2 exerted dual concentration-dependent stimulatory/inhibitory effects on store-operated, IP3 receptor-mediated and Orai1-mediated Ca(2+) entry, not coupled to vasoconstriction in coronary vascular smooth muscle. SOC entry activated by H2 O2 was enhanced and associated with vascular oxidative stress in coronary arteries in metabolic syndrome.
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Elvira
authors.initials: E
authors.lastname: Santiago
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Climent
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Muñoz
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Albino
authors.initials: A
authors.lastname: García-Sacristán
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Rivera
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Prieto
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D015220:Calcium Channels / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism; D000071740:ORAI1 Protein; D017208:Rats, Wistar; D011924:Rats, Zucker
chemical_list: D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D000071740:ORAI1 Protein; C532493:Orai1 protein, rat; D006861:Hydrogen Peroxide; D002118:Calcium