The effect of metoprolol on Calpain I and CaN signaling pathway in pressure overload induced myocardial hypertrophy / 天津医药

ABSTRACT

Objective To study the mechanism of metoprolol preventing pressure overload induced myocardial hypertrophy through inhibiting calcineurin (CaN) and CalpainⅠsignaling pathway in rat model of coarctation of abdominal aorta. Methods Thirty SD rats were used for hypertension rat model induced by coarctation of suprarenal abdominal aorta. Model rats were divided into three groups, sham operation group (n=10), abdominal aortic coarctation group (n=9) and metoprolol group (n=9). The changes of blood pressure [systolic blood pressure (SBP) and diastolic blood pressure (DBP)] and myocardial hypertrophy [the ratio of left ventricular mass/ body mass (LVW/BW)] were measured. RT-PCR was used to detect the expression of CaN mRNA, and Western blot assay was used to detect expressions of CaN and CalpainⅠproteins. The activity of CaN enzyme was detected and compared between three groups. Results Compared with the sham-operated sham operation group, values of SBP, DBP, LVW/BW, protein expressions and activities of CaN mRNA, CaN and CalpainⅠwere significantly increased in operation group (P<0.05). There were no significant differences in SBP and DBP between metoprolol-treated group and the operation group (P>0.05). Furthermore, values of SBP and DBP were significantly higher in metoprolol-treated group than those of sham group (P<0.05). Compared with operation group, values of LVW/BW, the protein expression and activity of CaN mRNA and Calpain Ⅰwere significantly decreased in metoprolol group (P<0.05), which were no significant differences compared with sham group. Conclusion Metoprolol prevents myocardial hypertrophy in abdominal aorta coarctative rats, through inhibiting CalpainⅠand CaN signaling pathways.