INVESTIGADORES
ENNIS Irene Lucia
artículos
Título:
Myocardial reperfusion injury: Reactive oxygen species vs. NHE-1 reactivation
Autor/es:
GARCIARENA CD; FANTINELLI, JC; CALDIZ CB; CHIAPPE DE CINGOLANI GE; 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:
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, p90(RSK), 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, p90(RSK), and
NHE-1 phosphorylation. MPG and cariporide cancelled these effects.
Sildenafil did not reduce the phosphorylated ERK1/2-p90(RSK) 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.