Carbonic anhydrase inhibition by benzolamide attenuates myocardial ischemia/reperfusion injury via p38MAPK-dependent mechanism

CIOCCI PARDO, A; GONZÁLEZ ARBELÁEZ LF; FANTINELLI JC; DÍAZ RG; ÁLVAREZ B; MOSCA SM

BUENOS AIRES

Congreso; XXII World Congress of the ISHR; 2016

Carbonic anhydrase (CA) catalyze the hydration of CO2 to H+ and HCO3-. During ischemia-reperfusion CO3H--dependent transporters participate of the intracellular pH (pHi) regulation, leading to Ca2+ overload. The involvement of CA in reperfusion injury has not been elucidated yet. Isolated rat hearts were submitted after 20-min stabilization to the following protocols: 1.-Ischemic control (IC): 30 min of global ischemia (GI) and 60 min of reperfusion (R); 2.- BZ: the CA inhibitor benzolamide (5 μM) was administered during the initial 10 min of R. To examine the participation of p38MAPK, SB202190 (10 μM) was perfused simultaneously to BZ. 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. The changes of pHi in papillary muscle by immunofluorescence were also determined. BZ decreased the IS (6.3 ± 0.6 % vs 32 ± 2 %, p < 0.05) and improved postischemic recovery of myocardial function. At the end of R LVDP was 69 ± 4 % vs. 15 ± 4 %; +dP/dtmax: 75 ± 5 % vs. 19 ± 5 %; LVEDP: 23 ± 3 vs. 52 ± 5 mmHg; -dP/dtmax: 72 ± 5 % vs. 17 ± 5 %, p < 0.05). The p38MAPK level increased after BZ treatment (189 ± 3 % vs. 53 ± 1 %, p < 0.05). BZ annulled pHi recovery from sustained intracellular acidosis (JH+ at pHi 6.8 in control was 0.102 ± 0.004 mmol/L x min-1). SB attenuated all the effects detected by BZ. The present data demonstrate that CA inhibition by BZ protects the heart against reperfusion injury through a p38MAPK-dependent pathway and suggest that an attenuation of Ca2+ overload could be the responsible mechanism.