CONICET | Buscador de Institutos y Recursos Humanos

Carbonic anhydrase (CA) is responsible for catalyzing the reversible hydration reaction of carbon dioxide to form proton and HCO3-. The activation of CO3H-dependent transporters during ischemia-reperfusion contributes to the Ca2+ overload and subsequent myocyte damage. Our objective was to determine the effects of CA inhibitor ethoxyzolamide on myocardial alterations produced by ischemia-reperfusion. Isolated rat hearts were submitted after 20 min of stabilization to the following protocols: 1.Non ischemic control (NIC): 90 min of perfusion; 2.Ischemic control (IC): 30 min of global ischemia (GI) and 60 min of reperfusion (R); 3.ETX: ethoxyzolamide 100 μM was administered during 10 min before ischemia and the initial 10 min of R. To examine the participation of p38MAPK, the protocols were repeated in presence of p38MAPK inhibitor SB202190 (10 μM) administered 10 min before ischemia. Infarct size (IS) was measured by TTC staining technique. Left ventricular developed pressure (LVDP), +dP/dtmax, left ventricular end diastolic pressure (LVEDP) and -dP/dtmax served to assess myocardial function. The p38MAPK expression was measured. ETX decreased the IS (12.0 ± 0.4 % vs. 32 ± 2 % in IC, p < 0.05) and improved postischemic recovery of myocardial function. At the end of R, LVDP was 62 ± 3 % vs. 15 ± 4 %; +dP/dtmax: 62 ± 4 % vs. 19 ± 5 %; LVEDP: 36 ± 5 vs. 52 ± 5 mmHg; -dP/dtmax: 60 ± 5 % vs. 17 ± 5 %, p < 0.05). The p38MAPK level increased after ETX treatment (153 ± 9 % vs. 74 ± 8 %, p < 0.05). SB attenuated the effects detected by ETX. The present data demonstrate that CA inhibitor ETX attenuates the post-ischemic myocardial dysfunction and decreases the cell death through p38MAPK-dependent pathways and suggest that an attenuation of Ca2+ overload could be the responsible mechanism.