Quenching the effects of L-arginine on free radical injury in cultured cardiomyocytes.
Neutrophil activation and oxygen-derived free radical formation have been implicated in cardiac ischemia-reperfusion injury. To elucidate the mechanism of ischemia-reperfusion injury, we thus determined the effect of the nitric oxide (NO) precursor L-arginine on the free radical injury of cultured cardiomyocytes which were obtained from patients undergoing corrective surgery for tetralogy of Fallot. Free radicals were generated from hypoxanthine via xanthine oxidase, and the cellular changes were determined microscopically. All concentrations of L-arginine (0.5 to 3 mM) prolonged the myocyte survival time compared to the control group, with 0.5 mM L-arginine increasing the survival time to the greatest extent. Cellular susceptibility to free radical injury was the lowest with 0.5 mM L-arginine. Further experiments were performed with 0.5 mM L-arginine plus 100 mM or 1000 mM of the NO synthase (NOS) inhibitor NG-nitro-L-arginine methylester (L-NAME) to determine whether or not the effects of L-arginine are mediated through the NO pathway. The survival time for the cells treated with a concentration of L-NAME was shorter than for the cells treated with 0.5 mM L-arginine alone. These results suggest that L-arginine acts through the NO-dependent pathway. In conclusion, our findings thus confirmed the quenching effects of NO on free radical injury in cultured cardiomyocytes.
Nonami
Y
Y
Department of Surgery II, Kochi Medical School, Kohasu, Nankoku, Japan.
Rao
V
V
Shiono
N
N
Ogoshi
S
S
D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology*; D002470:Cell Survival; D002478:Cells, Cultured; D005609:Free Radicals; D006801:Humans; D066298:In Vitro Techniques; D009206:Myocardium / Q000166:cytology* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress; D015427:Reperfusion Injury / Q000517:prevention & control*
D005609:Free Radicals; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase