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Cambios en la función ventricular sistólica y diastólica en un modelo de sobreexpresión cardíaca del receptor AT-1 de angiotensina;
Changes in Systolic and Diastolic Function in a Mouse Model Overexpressing Cardiac Angiotensin II AT-1 Receptor

Creators:Matorra, Luis F.; Revista de la Sociedad Argentina de Cardiología, Rey Deutsch, Ana Clara, Goyeneche, María Ailín, Garmendia, Cristian, Casanova, Verónica, Rando, Mariel, Celaya, Carla, Cicale, Eliana, Basso, Nidia
2013-12-11

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Descripción

La angiotensina II (Ang II) está involucrada en diferentes procesos fisiopatológicos, particularmente actuando sobre los receptores AT-1 de Ang II (AT1R). El objetivo de este trabajo fue evaluar la función ventricular sistólica y diastólica in vivo e in vitro en ratones con sobreexpresión cardíaca específica del receptor AT-1 de Ang II (AT1R). Un segundo objetivo fue determinar si el bloqueo agudo y crónico del AT1R revierte los cambios en la función ventricular.Se estudiaron ratones divididos en cuatro grupos experimentales. El primer grupo incluyó animales no transgénicos (NTG, n = 10), el segundo grupo ratones transgénicos (TG, n = 7) que sobreexpresan el AT1R solo a nivel cardíaco y el tercero y el cuarto grupos, animales TG tratados con losartán (L) durante 7 días (TG L7, n = 9) y 30 días (TG L30, n = 7), respectivamente. Los ratones TG presentaron hipertrofia ventricular izquierda (HVI). El tratamiento con losartán por 7 días no revirtió la HVI, lo que sí sucede cuando se extiende por 30 días. Los animales TG presentan una disminución significativa de la fracción de acortamiento, desde un valor de 47,1% ± 2,3% hasta 32,3% ± 1,3% (p &lt; 0,05), y de la +dP/dtmáx, que se reduce desde un valor de 7.073 ± 674 mm Hg hasta 3.897,5 ± 209,7 mm Hg/seg (p &lt; 0,05). El tratamiento con losartán por 7 y 30 días revierte esta disfunción sistólica.El tiempo de relajación isovolúmica y el t1/2 fueron de 24,1 ± 1,3 mseg y de 6,1 ± 0,5 mseg, respectivamente, en los NTG. Estos índices se incrementaron a 33,1 ± 2,2 mseg y a 8,4 ± 0,4 mseg, respectivamente, en los ratones TG (p &lt; 0,05). Esta alteración de la función diastólica fue revertida por completo con el tratamiento con losartán por 7 y 30 días. El análisis de la función ventricular in vitro con control de variables corroboró los hallazgos realizados in vivo.La sobreexpresión cardíaca de los AT1R induce una disfunción ventricular sistólica y diastólica que es revertida completamente por el bloqueo del AT1R. Este efecto beneficioso es independiente de modificaciones en la masa ventricular izquierda.

Angiotensin II (Ang II) is involved in various pathophysiological processes throughthe activation of angiotensin II AT-1 receptors. The purpose of this study was toassess in vivo and in vitro systolic and diastolic ventricular function in mice overexpressingthe cardiac-specific Ang II AT-1 receptor (AT1R). A second objective was todetermine whether ventricular function changes could be reversed with acute andchronic ATIR blockade.Mice were divided into four experimental groups. The first group included nontransgenicanimals (NTG, n=10), the second group consisted of transgenic mice (TG,n=7) with cardiac-specific AT1R overexpression and the third and fourth groupswere TG animals treated with losartan (L) for 7 (TG L7, n=9) and 30 days (TG L30,n=7), respectively. Transgenic animals exhibited left ventricular hypertrophy (LVH)which was only regressed with losartan treatment for 30 days. They also presented asignificant decrease in shortening fraction from 47.1±2.3% to 32.3±1.3% (p &lt;0.05)and of +dP/dtmax from 7073 ± 674 to 3897.5 ± 209.7 mmHg/sec (p&lt; 0.05). Systolicdysfunction recovered both with losartan treatment for 7 and 30 days.Isovolumic relaxation time and t1/2 were 24.1±1.3 and 5.1±0.5ms, respectively, inthe NTG group. These indexes increased to 33.1±2.2 and 8.4±0.4 ms, respectively,in TG mice (p&lt;0.05). Diastolic dysfunction was completely reversed by losartantreatment for 7 and 30 days. In vitro ventricular function with controlled variablesconfirmed in vivo findings.In conclusion, cardiac-specific AT1R overexpression induces systolic and diastolicventricular dysfunction which is completely reversed by AT1R blockade. This beneficialeffect is independent of left ventricular mass changes.

Metadatos destacados

Colecciones
Argentine Journal of Cardiology

Editor

Sociedad Argentina de Cardiología

Fuente

Revista Argentina de Cardiología; Vol 81, No 6 (2013); 473-479, Argentine Journal of Cardiology; Vol 81, No 6 (2013); 473-479

Citación

Matorra, Luis F.; Revista de la Sociedad Argentina de Cardiología et al., “Cambios en la función ventricular sistólica y diastólica en un modelo de sobreexpresión cardíaca del receptor AT-1 de angiotensina,” Archivo PPCT, consulta 1 de abril de 2026, http://archivoppct.caicyt.gov.ar/items/show/8357.

Dublin Core

Autor

Matorra, Luis F.; Revista de la Sociedad Argentina de Cardiología
Rey Deutsch, Ana Clara
Goyeneche, María Ailín
Garmendia, Cristian
Casanova, Verónica
Rando, Mariel
Celaya, Carla
Cicale, Eliana
Basso, Nidia

Fuente

Revista Argentina de Cardiología; Vol 81, No 6 (2013); 473-479
Argentine Journal of Cardiology; Vol 81, No 6 (2013); 473-479

Editor

Sociedad Argentina de Cardiología

Fecha

2013-12-11

Derechos

Los que firman al pié, certificamos que tenemos total responsabilidad por la conducción de este estudio y por el diseño y la interpretación de los datos. Nosotros escribimos el manuscrito y somos responsables por la decisión acerca del mismo. Cada uno de nosotros cumple la definición de autor como se afirma en el Comité Internacional de Editores de Revistas Médicas (International Committee of Medical Journal Editors, ver www.icmje.org). Nosotros hemos visto y aprobado el manuscrito final. Ni el artículo, ni ninguna parte esencial del mismo, incluido las tablas y las figuras, será publicado o admitido para arbitrar a otra parte antes de aparecer en la Revista.También notificamos haber leído la sección “conflicto de intereses”, y revelaríamos cualquiera que existiera. Dejamos constancia que si nuestro artículo se publicara en la RAC, cederíamos los derechos (copyright) a la Revista.Los documentos publicados en esta revista están bajo la licencia Creative Commons Atribución-NoComercial-Compartir-Igual 2.5 Argentina.
Those signing below certify that we have full responsibility for the conduction of this study and for the design and interpretation of the information. We wrote the manuscript and are responsible for its decision. Each of us fulfills the definition of authorship as stated by the International Committee of Medical Journal Editors ( www.icmje.org). We have signed and approved the final manuscript. Neither the manuscript, nor any essential part thereof, including tables and figures, will be published or accepted for refereeing elsewhere before being published in the Journal. We have also read the "Conflict of Interest" section and would disclose any existing. We state that if our manuscript is published in the RAC, we shall transfer the copyright to the Journal.

Formato

Idioma

spa
eng

Tipo

info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion