RESUMEN
The present study investigated whether dl-praeruptorin (Pd-Ia) prevents endothelin-1 (ET-1)-induced cardiomyocyte hypertrophy and the potential pathways that underlie such an effect. We assessed cardiomyocyte surface area, protein synthesis, the expression of Bax/Bcl2 and Jun genes, the expression of atrial natriuretic factor (ANF) and Ca2+/calmodulin-dependent kinase II (CaMK-II) activity in cultured neonatal rat ventricular cardiomyocytes with ET-1-induced hypertrophy. It was found that Pd-Ia decreased the surface area and protein synthesis rate in cardiomyocytes exposed to ET-1. Additionally, the expression of Bcl2 and Bax was increased in both the ET-1-exposed and Pd-Ia+ET- 1-treated groups compared with the control group, although this was not significant. In cardiomyocytes incubated with ET-1, the expression of ANF (Nppa) significantly increased relative to the control and Pd-Ia groups. The expression of Jun significantly increased in cardiomyocytes incubated with ET-1, but not in the Pd-Ia group, where Jun levels were similar to those found for the control group. Moreover, it was found that Pd-Ia inhibited the ET-1-induced increase in intracellular Ca(2+) concentration. The results showed that Pd-Ia could conceivably be an effective therapeutic drug for treating the contractile defects associated with cardiac hypertrophy and failure. This activity may be associated with its Ca2+-antagonist effect and modulation of the expression of immediate-early genes that play important roles in the mitogen-activated protein (MAP) kinase pathway.