The effect of tropisetron on expression of the pro-apoptotic factors in the rat model hypertrophic heart

Hypertension-induced left ventricular hypertrophy is an independent risk factor of heart failure and sudden death. Progression of cardiac hypertrophy is accompanied by activation of apoptosis signaling pathways. Tropisteron is a 5HT-3 receptor antagonist that its cardioprotective effects has been revealed by recent studies. Though, the underlying mechanisms are still unclear. The aim of the current study is to investigate the effect of tropisetron on gene expression of BNP (as the hypertrophy marker) and pro-apoptotic factors (BAD and BAX) in the rat model of hypertrophic heart.

Male Wistar rats (n = 24) were divided to the following groups: (I) control group including intact animals, (II) un-treated hypertrophy group (hypertrophy), (III) tropisetron-treated rats (3 mg/kg/day, 21 days)  during progression of hypertrophy (tropisetron + hypertrophy group), (IV) tropisetron-treated rats without induction of hypertrophy (tropisetron group). The left ventricular hypertrophy model was induced by surgical abdominal aortic banding. Gene expression was assessed by Real-time PCR.

cardiac BNP mRNA level increased significantly in Hypertrophy group compared to the control (p < 0.001). In the tropisetron + hypertrophy group, BNP mRNA level was decreased significantly when compared with un-treated Hypertrophy group (p < 0.05). The transcription level of BAD was also upregulated in left ventricle of un-treated hypertrophy group (p < 0.001 vs. control). However, in the Tropisetron+Hypertrophy group, BAD mRNA level was decreased significantly compared to the untreated hypertrophy group (p < 0.001). The transcription level of BAX did not change significantly among the experimental groups.

Tropisetron can prevent the progression of pressure overload-induced hypertrophy to heart failure at least in part by decreasing BAD expression.
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