Your browser doesn't support javascript.
loading
Bradykinin restores left ventricular function, sarcomeric protein phosphorylation, and e/nNOS levels in dogs with Duchenne muscular dystrophy cardiomyopathy.
Cardiovasc Res ; 95(1): 86-96, 2012 Jul 01.
Article en En | MEDLINE | ID: mdl-22562664
ABSTRACT

AIMS:

Cardiomyopathy is a lethal result of Duchenne muscular dystrophy (DMD), but its characteristics remain elusive. The golden retriever muscular dystrophy (GRMD) dogs produce DMD pathology and mirror DMD patient's symptoms, including cardiomyopathy. We previously showed that bradykinin slows the development of pacing-induced heart failure. Therefore, the goals of this research were to characterize dystrophin-deficiency cardiomyopathy and to examine cardiac effects of bradykinin in GRMD dogs. METHODS AND

RESULTS:

At baseline, adult GRMD dogs had reduced fractional shortening (28 ± 2 vs. 38 ± 2% in control dogs, P < 0.001) and left ventricular (LV) subendocardial dysfunction leading to impaired endo-epicardial gradient of radial systolic velocity (1.3 ± 0.1 vs. 3.8 ± 0.2 cm/s in control dogs, P < 0.001) measured by echocardiography. These changes were normalized by bradykinin infusion (1 µg/min, 4 weeks). In isolated permeabilized LV subendocardial cells of GRMD dogs, tension-calcium relationships were shifted downward and force-generating capacity and transmural gradient of myofilament length-dependent activation were impaired compared with control dogs. Concomitantly, phosphorylation of sarcomeric regulatory proteins and levels of endothelial and neuronal nitric oxide synthase (e/nNOS) in LV myocardium were significantly altered in GRMD dogs. All these abnormalities were normalized in bradykinin-treated GRMD dogs.

CONCLUSIONS:

Cardiomyopathy in GRMD dogs is characterized by profound LV subendocardial dysfunction, abnormal sarcomeric protein phosphorylation, and impaired e/nNOS, which can be normalized by bradykinin treatment. These data provide new insights into the pathophysiological mechanisms accounting for DMD cardiomyopathy and open new therapeutic perspectives.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sarcómeros / Bradiquinina / Proteínas / Función Ventricular Izquierda / Distrofia Muscular de Duchenne / Óxido Nítrico Sintasa de Tipo I / Óxido Nítrico Sintasa de Tipo III Límite: Animals Idioma: En Revista: Cardiovasc Res Año: 2012 Tipo del documento: Article País de afiliación: Francia

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sarcómeros / Bradiquinina / Proteínas / Función Ventricular Izquierda / Distrofia Muscular de Duchenne / Óxido Nítrico Sintasa de Tipo I / Óxido Nítrico Sintasa de Tipo III Límite: Animals Idioma: En Revista: Cardiovasc Res Año: 2012 Tipo del documento: Article País de afiliación: Francia