Effects of carvedilol on ventricular remodeling and the expression of β3-adrenergic receptor in a diabetic rat model subjected myocardial infarction.

BACKGROUND: This study was to assess effects of carvedilol on ventricular remodeling and expression of β3-adrenergic receptor (β3-AR) and Gi protein in a rat model of diabetes subjected to myocardial infarction (MI).

METHODS: Rat model of type II diabetes was established by injection of streptozotion. MI was then induced by ligating the left anterior descending coronary artery. Rats were then randomly divided into two groups treated with either placebo (PL) or carvedilol (CA - 10mg·kg(-1)·d(-)(1)). Additional controls consisted of sham-operated rats with diabetes (DS) and rats fed a normal diet subjected to myocardial infarction (NM). Echocardiographic and hemodynamic studies were performed to assess the structural and functional changes. β3-AR and Gi mRNA in the myocardium distal from the infarction region were measured, and β3-AR and Gi protein were measured with western blot.

RESULTS: There were no significant differences in MI size among the three MI groups. In the PL group, LVEDd, LVWI, E/A and CVF were significantly increased, while LVEF and PW% significantly decreased as compared with the DS and NM groups. Compared with the DS group, the expression of β3-AR and Gi mRNA and protein in the PL group was significantly increased, however, in the CA group, β3-AR and Gi mRNA and protein were decreased.

CONCLUSIONS: The expression of β3-AR and Gi mRNA and protein was increased in diabetic rats subjected to MI as compared with rats subject to either condition alone. Carvedilol treatment prevented many of these deleterious effects.