Enalapril Induces Regression of Cardiac Hypertrophy and Normalization of pH<sub>i</sub> Regulatory Mechanisms

Intracellular pH is under strict control in myocardium; H⁺ are extruded from the cells by sodium-dependent mechanisms, mainly Na⁺ /H⁺ exchanger and Na⁺ /HCO₃⁻ symport, whereas Na⁺ -independent Cl⁻ /HCO₃⁻ exchanger extrudes bases on intracellular alkalinization. Hypertrophic myocardium from spontaneo...

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Autores principales: Ennis, Irene Lucía, Álvarez, Bernardo Víctor, Camilión de Hurtado, María Cristina, Cingolani, Horacio Eugenio
Formato: Articulo
Lenguaje:Inglés
Publicado: 1998
Materias:
Medicina
ion transport
hypertrophy, cardiac
angiotensin-converting enzyme inhibitors
protein kinase C
intracellular pH
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/122866
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-122866
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Medicina
ion transport
hypertrophy, cardiac
angiotensin-converting enzyme inhibitors
protein kinase C
intracellular pH
spellingShingle Medicina
ion transport
hypertrophy, cardiac
angiotensin-converting enzyme inhibitors
protein kinase C
intracellular pH
Ennis, Irene Lucía
Álvarez, Bernardo Víctor
Camilión de Hurtado, María Cristina
Cingolani, Horacio Eugenio
Enalapril Induces Regression of Cardiac Hypertrophy and Normalization of pH<sub>i</sub> Regulatory Mechanisms
topic_facet Medicina
ion transport
hypertrophy, cardiac
angiotensin-converting enzyme inhibitors
protein kinase C
intracellular pH
description Intracellular pH is under strict control in myocardium; H⁺ are extruded from the cells by sodium-dependent mechanisms, mainly Na⁺ /H⁺ exchanger and Na⁺ /HCO₃⁻ symport, whereas Na⁺ -independent Cl⁻ /HCO₃⁻ exchanger extrudes bases on intracellular alkalinization. Hypertrophic myocardium from spontaneously hypertensive rats (SHR) exhibits increased Na⁺ /H⁺ exchange activity that is accompanied by enhanced extrusion of bases through Na⁺ -independent Cl⁻ /HCO₃⁻ exchange. The present experiments were designed to investigate the effect of enalapril-induced regression of cardiac hypertrophy on the activity of these exchangers. Male SHR and normotensive Wistar-Kyoto rats (WKY) received enalapril maleate (20 mg/kg per day) in the drinking water for 5 weeks. Gender- and age-matched SHR and WKY were used as untreated controls. Enalapril treatment significantly reduced systolic blood pressure in SHR and completely regressed cardiac hypertrophy. Na⁺ /H⁺ activity was estimated in terms of both steady pH<sub>i</sub> value in HEPES buffer and the rate of pH<sub>i</sub> recovery from CO₂ -induced acid load. Na⁺ -independent Cl⁻ /HCO₃⁻ activity was assessed by measuring the rate of pH<sub>i</sub> recovery from intracellular alkalinization produced by trimethylamine exposure. Regression of cardiac hypertrophy was accompanied by normalization of Na⁺ /H⁺ and Na⁺ -independent Cl⁻ /HCO₃⁻ exchange activities. Inhibition of protein kinase C (PKC) activity with chelerythrine (10 mmol/L) or calphostin C (50 nmol/L) returned both exchange activities to normal values. These results show that angiotensin-converting enzyme inhibition normalizes the enhanced activity of both exchangers while regressing cardiac hypertrophy. Because normalization of exchange activities could be also achieved by PKC inhibition, the data would suggest that PKC-dependent mechanisms play a significant role in the increased ion exchange activities of hypertrophic myocardium and in their normalization by angiotensin-converting enzyme inhibition.
format Articulo
Articulo
author Ennis, Irene Lucía
Álvarez, Bernardo Víctor
Camilión de Hurtado, María Cristina
Cingolani, Horacio Eugenio
author_facet Ennis, Irene Lucía
Álvarez, Bernardo Víctor
Camilión de Hurtado, María Cristina
Cingolani, Horacio Eugenio
author_sort Ennis, Irene Lucía
title Enalapril Induces Regression of Cardiac Hypertrophy and Normalization of pH<sub>i</sub> Regulatory Mechanisms
title_short Enalapril Induces Regression of Cardiac Hypertrophy and Normalization of pH<sub>i</sub> Regulatory Mechanisms
title_full Enalapril Induces Regression of Cardiac Hypertrophy and Normalization of pH<sub>i</sub> Regulatory Mechanisms
title_fullStr Enalapril Induces Regression of Cardiac Hypertrophy and Normalization of pH<sub>i</sub> Regulatory Mechanisms
title_full_unstemmed Enalapril Induces Regression of Cardiac Hypertrophy and Normalization of pH<sub>i</sub> Regulatory Mechanisms
title_sort enalapril induces regression of cardiac hypertrophy and normalization of ph<sub>i</sub> regulatory mechanisms
publishDate 1998
url http://sedici.unlp.edu.ar/handle/10915/122866
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