Inhibitory effects of antioxidants on neonatal rat cardiac myocyte hypertrophy induced by tumor necrosis factor-alpha 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 that TNF-alpha and Ang II might cause myocyte hypertrophy via the generation of ROIs.


RESULTS
To test the hypothesis, we tested whether TNF-alpha and Ang II could induce the generation of ROIs and whether antioxidants such as butylated hydroxyanisole (BHA), vitamin E, and catalase might inhibit the hypertrophy in cultured neonatal rat cardiac myocytes. ROIs were measured by the ROI-specific probe 2',7'-dichlorofluorescin diacetate in cultured cardiac myocytes. We demonstrated that TNF-alpha and Ang II induced the generation of ROIs in a dose-dependent manner. TNF-alpha (10 ng/mL) and Ang II (100 nmol/L) enlarged cardiac myocytes and increased [3H]leucine uptake, and BHA (10 micromol/L) significantly inhibited both effects. Other antioxidants, such as vitamin E (1 microg/mL) and catalase (100 U/mL), also inhibited the enlargement of cardiac myocytes induced by TNF-alpha.


CONCLUSIONS
These results indicate that TNF-alpha and Ang II cause hypertrophy in part via the generation of ROIs in cardiac myocytes.
Nakamura
K
K
Department of Cardiovascular Medicine, Okayama University Medical School, Japan. cardio@cc.okayama-u.ac.jp
Fushimi
K
K
Kouchi
H
H
Mihara
K
K
Miyazaki
M
M
Ohe
T
T
Namba
M
M
D000804:Angiotensin II / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000627:therapeutic use*; D002083:Butylated Hydroxyanisole / Q000627:therapeutic use; D006332:Cardiomegaly / Q000139:chemically induced / Q000188:drug therapy*; D002374:Catalase / Q000627:therapeutic use; D002478:Cells, Cultured; D007930:Leucine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000633:toxicity; D014316:Tritium; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*; D014810:Vitamin E / Q000627:therapeutic use
D000975:Antioxidants; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D014316:Tritium; D000804:Angiotensin II; D014810:Vitamin E; D002083:Butylated Hydroxyanisole; D002374:Catalase; D007930:Leucine