The possible role of caspase-3 in pathological and physiological cardiac hypertrophy in rats

The present study has been designed to investigate the effect of Ac-DEVD-CHO, a specific caspase-3 inhibitor in partial abdominal aortic constriction for 4 week-induced pathological and chronic swimming training for 8 week-induced physiological cardiac hypertrophy. Ac-DEVD-CHO (2 mg/kg intraperitoneally, day(-1))treatment was started three days before partial abdominal aortic constriction and chronic swimming test and it was continued for 4 weeks in partial abdominal aortic constriction and 8 weeks in chronic swimming test experimental model. The left ventricular (LV) function and LV hypertrophy were assessed by measuring LV developed pressure, dp/dt(max), dp/dt(min), ratio of LV weight to body weight, LV wall thickness, LV collagen content, protein content and RNA concentration. Further, venous pressure and mean arterial blood pressure were recorded. The partial abdominal aortic constriction but not chronic swimming test produced LV dysfunction by decreasing LV developed pressure, dp/dtmax, dp/dtmin. and increasing LV collagen content. Further, partial abdominal aortic constriction and chronic swimming test were noted to produce LV hypertrophy by increasing ratio of LV weight to body weight, LV wall thickness, LV protein content and LV RNA concentration. Moreover, in contrast to chronic swimming test, partial abdominal aortic constriction has significantly increased venous pressure and mean arterial blood pressure. The Ac-DEVD-CHO has markedly attenuated partial abdominal aortic constriction-induced LV dysfunction, LV hypertrophy, increase in venous pressure and mean arterial blood pressure. However it did not modulate chronic swimming test-induced LV hypertrophy. These results have implicated caspase-3 in partial abdominal aortic constriction-induced LV dysfunction and pathological cardiac hypertrophy. However, caspase-3 may not be involved in chronic swimming test-induced physiological cardiac hypertrophy.