The Possible Role of TNF-α in Physiological and Pathophysiological Cardiac Hypertrophy in Rats

Pathological cardiac hypertrophy was produced by partial abdominal aortic constriction (PAAC) for 4 wk, while physiological cardiac hypertrophy was produced by chronic swimming training (CST) for 8 wk in rats. Pentoxifylline (30 mg/kg, 300 mg/kg i.p., day) treatment was started three days before PAAC and CST and it was continued for 4 wk in PAAC and 8 wk in CST experimental model. The left ventricular (LV) hypertrophy was assessed by measuring ratio of LV weight to body weight, LV wall thickness, LV protein content and LV RNA concentration. Further venous pressure (VP) and mean arterial blood pressure (MABP) were recorded. Moreover, DNA gel electrophoresis was employed to assess the myocardial cell death. The PAAC and CST were noted to increase the ratio of LV weight to body weight, LV wall thickness, LV protein content and LV RNA concentration. Further PAAC but not CST significantly increased VP, MABP and LV necrotic cell death. Pentoxifylline, a TNF-α inhibitor markedly attenuated PAAC induced increase in LV hypertrophy, VP, MABP and LV necrotic cell death; but it did not modulate CST induced LV hypertrophy. These results implicate TNF-α in PAAC induced cell death and pathological cardiac hypertrophy. However, TNF-α may not be involved in CST induced physiological cardiac hypertrophy.