RESUMEN

To examine the response to chronic high-dose angiotensin II (Ang II) and a proposed milder response in female hearts with respect to gene expression and ischemic injury. Female and male litter-matched rats were treated with 400 ng kg(-1) min(-1) Ang II for 14 days. Hearts were isolated, subjected to 30-min ischemia and 30-min reperfusion in combination with functional monitoring and thereafter harvested for gene expression, WB and histology. Ang II-treated hearts showed signs of non-hypertrophic remodeling and had significantly higher end diastolic pressure after reperfusion, but no significant gender difference was detected. Ang II increased expression of genes related to heart function (ANF, ß-MCH, Ankrd-1, PKC-α, PKC-δ TNF-α); fibrosis (Col I-α1, Col III-α1, Fn-1, Timp1) and apoptosis (P53, Casp-3) without changing heart weight but with 68% increase in collagen content. High (sub-toxic) dose of Ang II resulted in marked heart remodeling and diastolic dysfunction after ischemia without significant myocyte hypertrophy or ventricular chamber dilatation. Although there were some gender-dependent differences in gene expression, female gender did not protect against the overall response.

Asunto(s)

Angiotensina II/administración & dosificación , Regulación de la Expresión Génica , Daño por Reperfusión Miocárdica/prevención & control , Miocardio/metabolismo , Función Ventricular Izquierda/genética , Animales , Apoptosis/genética , Colágeno/metabolismo , Modelos Animales de Enfermedad , Femenino , Fibrosis , Bombas de Infusión Implantables , Infusiones Subcutáneas , Masculino , Daño por Reperfusión Miocárdica/genética , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/fisiopatología , Miocardio/patología , Ratas , Ratas Endogámicas BN , Ratas Endogámicas F344 , Recuperación de la Función , Factores Sexuales , Factores de Tiempo , Presión Ventricular/genética