INHIBITORY EFFECTS OF ANTIOXIDANTS ON NEONATAL RAT CARDIAC MYOCYTE HYPERTROPHY INDUCED BY TUMOR NECROSIS FACTOR-A AND ANGIOTENSIN-II

Background-Tumor necrosis factor-alpha (TNF-alpha) and angiotensin II (Ang II) modulate heart failure in part by provoking the hypertrophic response. Signal transduction pathways of those factors are implicated in reactive oxygen intermediates (ROIs), Therefore, we hypothesized t hat TNF-alpha and Ang Il might cause myocyte hypertrophy via the gener ation of ROIs. Methods and Results-To test the hypothesis, we tested w hether TNF-alpha and Ang II could induce the generation of ROIs and wh ether antioxidants such as butylated hydroxyanisole (BHA), vitamin E, and catalase might inhibit the hypertrophy in cultured neonatal rat ca rdiac myocytes. ROIs were measured by the ROI-specific probe 2',7'-dic hlorofluorescin diacetate in cultured cardiac myocytes. We demonstrate d that TNF-alpha and Ang II induced the generation of ROIs in a dose-d ependent manner. TNF-alpha (10 ng/mL) and Ang II (100 nmol/L) enlarged cardiac myocytes and increased [H-3]leucine uptake, and BHA (10 mu mo l/L) significantly inhibited both effects. Other antioxidants, such as vitamin E (1 mu g/mL) and catalase (100 U/mL), also inhibited the enl argement of cardiac myocytes induced by TNF-alpha. Conclusions-These r esults indicate that TNF-alpha and Ang II cause hypertrophy in part vi a the generation of ROIs in cardiac myocytes.