Benzolamide perpetuates acidic conditions during reperfusion and reduces myocardial ischemia-reperfusion injury

During ischemia, increased anaerobic glycolysis results in intracellular acidosis. Activation of alkalinizing transport mechanisms associated with carbonic anhydrases (CAs) leads to myocardial intracellular Ca²⁺ increase. We characterize the effects of inhibition of CA with benzolamide (BZ) during c...

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Detalles Bibliográficos
Autores principales: Ciocci Pardo, Alejandro, Díaz, Romina Gisel, González Arbeláez, Luisa Fernanda, Pérez, Néstor Gustavo, Swenson, Erik R., Mosca, Susana María, Álvarez, Bernardo Víctor
Formato: Articulo
Lenguaje:Inglés
Publicado: 2018
Materias:
Ciencias Médicas
Acidic reperfusion
Benzolamide
Carbonic anhydrase
Mitochondria
Myocardial infarction
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/136313
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-136313
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
Acidic reperfusion
Benzolamide
Carbonic anhydrase
Mitochondria
Myocardial infarction
spellingShingle Ciencias Médicas
Acidic reperfusion
Benzolamide
Carbonic anhydrase
Mitochondria
Myocardial infarction
Ciocci Pardo, Alejandro
Díaz, Romina Gisel
González Arbeláez, Luisa Fernanda
Pérez, Néstor Gustavo
Swenson, Erik R.
Mosca, Susana María
Álvarez, Bernardo Víctor
Benzolamide perpetuates acidic conditions during reperfusion and reduces myocardial ischemia-reperfusion injury
topic_facet Ciencias Médicas
Acidic reperfusion
Benzolamide
Carbonic anhydrase
Mitochondria
Myocardial infarction
description During ischemia, increased anaerobic glycolysis results in intracellular acidosis. Activation of alkalinizing transport mechanisms associated with carbonic anhydrases (CAs) leads to myocardial intracellular Ca²⁺ increase. We characterize the effects of inhibition of CA with benzolamide (BZ) during cardiac ischemia-reperfusion (I/R). Langendorff-perfused isolated rat hearts were subjected to 30 min of global ischemia and 60 min of reperfusion. Other hearts were treated with BZ (5 μM) during the initial 10 min of reperfusion or perfused with acid solution (AR, pH 6.4) during the first 3 min of reperfusion. p38MAPK, a kinase linked to membrane transporters and involved in cardioprotection, was examined in hearts treated with BZ in presence of the p38MAPK inhibitor SB202190 (10 μM). Infarct size (IZ) and myocardial function were assessed, and phosphorylated forms of p38MAPK, Akt, and PKCε were evaluated by immunoblotting. We determined the rate of intracellular pH (pHi) normalization after transient acid loading in the absence and presence of BZ or BZ + SB202190 in heart papillary muscles (HPMs). Mitochondrial membrane potential (ΔΨm), Ca²⁺ retention capacity and Ca²⁺-mediated swelling after I/R were also measured. BZ, similarly to AR, reduced IZ, improved postischemic recovery of myocardial contractility, increased phosphorylation of Akt, PKCε, and p38MAPK, and normalized ΔΨm and Ca²⁺ homeostasis, effects abolished after p38MAPK inhibition. In HPMs, BZ slowed pHi recovery, an effect that was restored after p38MAPK inhibition. We conclude that prolongation of acidic conditions during reperfusion by BZ could be responsible for the cardioprotective benefits of reduced infarction and better myocontractile function, through p38MAPK-dependent pathways.
format Articulo
Articulo
author Ciocci Pardo, Alejandro
Díaz, Romina Gisel
González Arbeláez, Luisa Fernanda
Pérez, Néstor Gustavo
Swenson, Erik R.
Mosca, Susana María
Álvarez, Bernardo Víctor
author_facet Ciocci Pardo, Alejandro
Díaz, Romina Gisel
González Arbeláez, Luisa Fernanda
Pérez, Néstor Gustavo
Swenson, Erik R.
Mosca, Susana María
Álvarez, Bernardo Víctor
author_sort Ciocci Pardo, Alejandro
title Benzolamide perpetuates acidic conditions during reperfusion and reduces myocardial ischemia-reperfusion injury
title_short Benzolamide perpetuates acidic conditions during reperfusion and reduces myocardial ischemia-reperfusion injury
title_full Benzolamide perpetuates acidic conditions during reperfusion and reduces myocardial ischemia-reperfusion injury
title_fullStr Benzolamide perpetuates acidic conditions during reperfusion and reduces myocardial ischemia-reperfusion injury
title_full_unstemmed Benzolamide perpetuates acidic conditions during reperfusion and reduces myocardial ischemia-reperfusion injury
title_sort benzolamide perpetuates acidic conditions during reperfusion and reduces myocardial ischemia-reperfusion injury
publishDate 2018
url http://sedici.unlp.edu.ar/handle/10915/136313
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