Exercise and tachycardia increase NADPH oxidase and ryanodine receptor-2 activity: possible robe in cardioprotection

Sánchez G; Escobar M.; pedrozo, Z; Macho P; Domenech, R; Hartel, S; Hidalgo C.; Donoso P.

Abstract

Aim: Our objective was to investigate in cardiac muscle the contribution of NADPH oxidase to (a) ryanodine receptor-2 (RyR2) S-glutathionylation and (b) the preconditioning effects of exercise and tachycardia on infarct size following coronary artery occlusion. Methods and results: We measured NADPH oxidase activity, RyR2 S-glutathionylation, and calcium release kinetics in sarcoplasmic reticulum (SR) vesicles isolated from dog ventricular muscle after exercise and tachycardia, plus or minus prior administration of the NADPH oxidase inhibitor apocynin. In ventricular muscle sections, we studied the colocalization of NADPH oxidase and RyR2 by confocal microscopy using fluorescent antibodies. We determined the effect of apocynin on the infarct size produced by occlusion of the descendent anterior coronary artery in animals preconditioned by exercise or tachycardia. Exercise and tachycardia increased NADPH oxidase activity, RyR2 S-glutathionylation, and calcium release rates in isolated SR vesicles. Cardiac muscle sections displayed significant colocalization of NADPH oxidase and RyR2, suggesting direct and specific effects of reactive oxygen species (ROS) produced by NADPH oxidase on RyR2 activation. The NADPH oxidase inhibitor apocynin prevented the increase in RyR2 S-glutathionylation, reduced calcium release activity, and completely prevented the protective effects of exercise and tachycardia on infarct size. Conclusions: The loss of cardioprotection induced by the NADPH oxidase inhibitor suggests that ROS generated by this enzyme are important mediators of the preconditioning response, which presumably involves NADPH oxidase-induced RyR2 S-glutathionylation. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2007.

Más información

Título según WOS: Exercise and tachycardia increase NADPH oxidase and ryanodine receptor-2 activity: possible robe in cardioprotection
Título según SCOPUS: Exercise and tachycardia increase NADPH oxidase and ryanodine receptor-2 activity: Possible role in cardioprotection
Título de la Revista: CARDIOVASCULAR RESEARCH
Volumen: 77
Número: 2
Editorial: OXFORD UNIV PRESS
Fecha de publicación: 2008
Página de inicio: 380
Página final: 386
Idioma: English
URL: http://cardiovascres.oxfordjournals.org/cgi/doi/10.1093/cvr/cvm011
DOI:

10.1093/cvr/cvm011

Notas: ISI, SCOPUS