Reduction of isoproterenol-induced cardiac hypertrophy and modulation of myocardial connexin43 by a KATP channel agonist.
Mol Med Rep
; 11(3): 1845-50, 2015 Mar.
Article
em En
| MEDLINE
| ID: mdl-25411819
Cardiac hypertrophy is a compensatory mechanism that occurs in conjunction with cardiovascular diseases. Although hypertrophy of the myocardium provides certain benefits during the early stages of cardiovascular disease, prolonged hypertrophy is potentially harmful to the heart and can result in arrhythmia and heart failure. The aim of this study was to investigate whether an ATPsensitive K+ (KATP) channel agonist was capable of reducing isoproterenol (Iso)induced cardiac hypertrophy and modulating myocardial connexin43 (Cx43) expression. Fifty male Sprague Dawley rats were randomly assigned to five groups: Normal, vehicle, nicorandil, glibenclamide and nicorandil plus glibenclamide. Rats in the four treatment groups received Iso injection for seven days, followed by administration with saline, nicorandil, glibenclamide or a combination of nicorandil and glibenclamide, respectively, for four weeks. Cardiac hypertrophy was then evaluated by measuring body weight, heart weight and leftventricular weight, and plasma Btype natriuretic peptide levels were evaluated by ELISA. Immunocytochemistry and a reverse transcriptionpolymerase chain reaction were performed to detect the spatial distribution and gene expression of myocardial Cx43, respectively. The KATP channel agonist nicorandil markedly attenuated the degree of myocardial hypertrophy induced by Iso as compared with the vehicle group. Myocardial Cx43 expression was significantly decreased and redistributed following cardiac hypertrophy. The decrease and redistribution of Cx43 was reduced following treatment with the KATP channel agonist nicorandil. Addition of the KATP channel blocker glibenclamide eliminated the beneficial effects of nicorandil against hypertrophy and on connexin43. In conclusion, the present study indicated that chronic use of KATP channel agonists following cardiac hypertrophy can attenuate ventricular remodeling and upregulate the expression level and spatial distribution of Cx43.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cardiomegalia
/
Conexina 43
/
Canais KATP
/
Isoproterenol
/
Miocárdio
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article