%0 Journal Article
%A Santiago Prieto, María Elvira
%A Climent Flórez, Belén
%A Muñoz Picos, Mercedes
%A García Sacristán, Albino
%A Rivera De Los Arcos, Luis
%A Prieto Ocejo, Dolores
%T Hydrogen peroxide activates store-operated Ca2+ entry in coronary arteries
%D 2015
%@ 1476-5381
%U https://hdl.handle.net/20.500.14352/101355
%X BACKGROUND AND PURPOSEAbnormal Ca2+ metabolism has been involved in the pathogenesis of vascular dysfunction associated with oxidative stress. Here, we have investigated the actions of H2O2 on store-operated Ca2+ (SOC) entry in coronary arteries and assessed whether it is impaired in arteries from a rat model of metabolic syndrome.EXPERIMENTAL APPROACHSimultaneous measurements of intracellular Ca2+ concentration and contractile responses were made in coronary arteries from Wistar and obese Zucker rats, mounted in microvascular myographs, and the effects of H2O2 were assessed.KEY RESULTSH2O2 raised intracellular Ca2+ concentrations, accompanied by simultaneous vasoconstriction that was markedly reduced in a Ca2+-free medium. Upon Ca2+ re-addition, a nifedipine-resistant sustained Ca2+ entry, not coupled to contraction, was obtained in endothelium-denuded coronary arteries. The effect of H2O2 on this voltage-independent Ca2+ influx was concentration dependent, and high micromolar H2O2 concentrations were inhibitory and reduced SOC entry evoked by inhibition of the sarcoplasmic reticulum ATPase (SERCA). H2O2-induced increases in Fura signals were mimicked by Ba2+ and reduced by heparin, Gd3+ ions and by Pyr6, a selective inhibitor of the Orai1-mediated Ca2+ entry. In coronary arteries from obese Zucker rats, intracellular Ca2+ mobilization and SOC entry activated by acute exposure to H2O2 were augmented and associated with local oxidative stress.CONCLUSION AND IMPLICATIONSH2O2 exerted dual concentration-dependent stimulatory/inhibitory effects on store-operated, IP3 receptor-mediated and Orai1-mediated Ca2+ entry, not coupled to vasoconstriction in coronary vascular smooth muscle. SOC entry activated by H2O2 was enhanced and associated with vascular oxidative stress in coronary arteries in metabolic syndrome.
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