CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
Beta-adrenergic stimulation is involved in the contractile dysfunction of the stunned heart
VITTONE L; SAID M; MATTIAZZI A
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
Año: 2006 vol. 373 p. 60 - 70
Endogenous catecholamines released during myocardial ischemia have been considered both, to aggravate cell injury and exacerbate arrhythmias or to exert a protective action on the post-ischemic contractile function. The present work was addressed to look for evidence to explain this controversy. The effects of cardiac catecholamine depletion and of a- and ©¬-adrenoceptor (AR) blockade on the post-ischemic contractile dysfunction as well as on its possible relationship with cardiac oxidative stress, were studied in isolated and perfused rat hearts, submitted to 20 min of ischemia and 30 min of reperfusion (stunning). Catecholamine depletion improves the contractile recovery in the stunned heart. This mechanical effect was associated with decreased levels of lipid peroxidation. A similar enhancement of the contractile function during reperfusion was detected after the simultaneous blockade of a1- and ©¬-ARs with prazosin plus propranolol. To dissect which specific ARs-pathway was involved in the effects of catecholamines on the stunned heart, selective ARs blockers, prazosin (a1-blocker), atenolol (©¬1-blocker), ICI 118,551 (©¬2-blocker) as well as selective inhibitors of Gi-PI3K pathway (pertussis toxin and wortmannin) were alternatively combined. The results indicate that catecholamines released during ischemia exert a dual action on the contractile behavior of the stunned heart: A deleterious effect, related to the activation of the ©¬2-AR-Gi-PI3K-pathway, which was counteracted by a beneficial effect, triggered by the stimulation of ¥á1-AR. Neither the depression nor the enhancement of the post-ischemic contractile recovery were related with the increase in ROS formation induced by endogenous catecholamines