CIC   05421
CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
artículos
Título:
Myocardial reperfusion injury: Reactive oxygen species vs. NHE-1 reactivation
Autor/es:
C GARCIARENA; FANTINELLI JC; C CALDIZ; GLADYS E CHIAPPE DE CINGOLANI; ENNIS IL; PÉREZ NG; CINGOLANI HE; MOSCA SM
Revista:
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY : INTERNATIONAL JOURNAL OF EXPERIMENTAL CELLULAR PHYSIOLOGY, BIOCHEMISTRY, AND PHARMACOLOGY.
Editorial:
KARGER
Referencias:
Lugar: Basel; Año: 2011 vol. 27 p. 13 - 22
ISSN:
1015-8987
Resumen:
Background/Aims: Flow restoration to ischemic myocardium
reduces infarct size (IS), but it also promotes
reperfusion injury. A burst of reactive oxygen species
(ROS) and/or NHE-1 reactivation were proposed to
explain this injury. Our study was aimed to shed light
on this unresolved issue. Methods: Regional infarction
(40 min-ischemia/2 hs-reperfusion) was induced
in isolated and perfused rat hearts. Maximal doses of
N-(2-mercaptopropionyl)-glycine (MPG 2mmol/L, ROS
scavenger), cariporide (10μmol/L, NHE-1 inhibitor),
or sildenafil (1μmol/L, phosphodiesterase5A inhibitor)
were applied at reperfusion onset. Their effects
on IS, myocardial concentration of thiobarbituric acid
reactive substances (TBARS), ERK1/2, p90RSK, and
NHE-1 phosphorylation were analyzed. Results: All
treatments decreased IS ~ 50% vs. control. No further
protection was obtained by combining cariporide
or MPG with sildenafil. Myocardial TBARS increased
after infarction and were decreased by MPG or
cariporide, but unaffected by sildenafil. In line with
the fact that ROS induce MAPK-mediated NHE-1 activation,
myocardial infarction increased ERK1/2,
p90RSK, and NHE-1 phosphorylation. MPG and
cariporide cancelled these effects. Sildenafil did not
reduce the phosphorylated ERK1/2-p90RSK levels but
blunted NHE-1 phosphorylation suggesting a direct
dephosphorylating action. Conclusions: 1)
Reperfusion injury would result from ROS-triggered
MAPK-mediated NHE-1 phosphorylation (and reactivation)
during reperfusion; 2) sildenafil protects the
myocardium by favouring NHE-1 dephosphorylation
and bypassing ROS generation