CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Carbonic anhydrase inhibition by benzolamide attenuates myocardial ischemia/reperfusion injury via p38MAPK-dependent mechanism
CIOCCI PARDO A; DIAZ RG; GONZALEZ ARBELAEZ LF; ÁLVAREZ BV; FANTINELLI JC; MOSCA SM
Congreso; ISHR XXII World Congress; 2016
International Society of Heart Research
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 stabilizationto the following protocols: 1.-Ischemic control (IC): 30 min of global ischemia (GI) and 60 min of reperfusion (R); 2.-BZ: the CAinhibitor 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/dtmaxserved to assess myocardial function. The p38MAPKexpression was measured. The changes ofpHi in papillary muscle by immunofluorescencewere also determined.BZ decreased the IS (6.3 ± 0.6 % vs 32 ± 2 %, p < 0.05) and improved postischemicrecovery of myocardial function. At the end of R LVDP was69 ± 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 was0.102 ± 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 theresponsible mechanism.