RT Journal Article
T1 Hydrogen peroxide activates store-operated Ca2+ entry in coronary arteries
A1 Santiago Prieto, María Elvira
A1 Climent Flórez, Belén
A1 Muñoz Picos, Mercedes
A1 García Sacristán, Albino
A1 Rivera De Los Arcos, Luis
A1 Prieto Ocejo, Dolores
AB 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.
PB WILEY
SN 1476-5381
YR 2015
FD 2015-10-24
LK https://hdl.handle.net/20.500.14352/101355
UL https://hdl.handle.net/20.500.14352/101355
LA eng
NO Santiago, Elvira, et al. «Hydrogen Peroxide Activates Store‐operated Ca 2+ Entry in Coronary Arteries». British Journal of Pharmacology, vol. 172, n.o 22, noviembre de 2015, pp. 5318-32. DOI.org (Crossref), https://doi.org/10.1111/bph.13322.
NO Ministerio de Economía, Comercio y Empresa (España)
DS Docta Complutense
RD 18 abr 2025