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Can J Physiol Pharmacol ; 88(10): 949-59, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20962894

RESUMO

Dysfunction of capsaicin-sensitive sensory nerves is involved in cardiac remodeling, and rutaecarpine has been shown to exert a beneficial effect on cardiac function through activating the sensory nerves. This study was conducted to explore the potential inhibitory effect of rutaecarpine on cardiac remodeling and the underlying mechanisms. A rat cardiac remodeling model was established by injection of isoprenaline (5 mg/kg per day, s.c.) for 10 days. Rutaecarpine (10 or 40 mg/kg, i.g.) was coadministrated with isoprenaline to evaluate the effect of rutaecarpine on cardiac remodeling. After echocardiographic analysis was performed, blood samples were collected to quantify calcitonin gene-related peptide (CGRP), dorsal root ganglia were isolated for examining CGRP mRNA expression, and the hearts were weighed and saved for evaluating the parameters related to apoptosis and hypertrophy. Isoprenaline significantly increased the ratio of left ventricle weight to body weight, the cross-sectional area of cardiomyocytes, cardiac apoptosis, and collagen deposition concomitantly with decreased CGRP production, which were reversed by rutaecarpine treatment. The beneficial effects of rutaecarpine were attenuated by pretreatment with capsaicin, which selectively depleted CGRP. These results suggest that rutaecarpine was able to reverse isoprenaline-induced cardiac remodeling through stimulating CGRP production.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina/biossíntese , Ventrículos do Coração/efeitos dos fármacos , Alcaloides Indólicos/farmacologia , Isoproterenol/farmacologia , Quinazolinas/farmacologia , Remodelação Ventricular/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Peptídeo Relacionado com Gene de Calcitonina/sangue , Ecocardiografia , Gânglios Espinais/metabolismo , Ventrículos do Coração/inervação , Marcação In Situ das Extremidades Cortadas , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa
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