Nitric oxide as an inflammatory mediator of radiation pneumonitis in rats.
Radiation pneumonitis is a major complication of radiation therapy. To elucidate the mechanisms of radiation-induced pneumonitis, we studied nitric oxide (NO) produced from lung tissues using a model of unilaterally irradiated rats. Our results demonstrated that alveolar macrophages (AM) produced NO after irradiation, and the expression of inducible NO synthase (NOS) in both AM and alveolar epithelial cells was increased. Furthermore, the progression of radiation pneumonitis was reduced with the in vivo treatment of the NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). The effect of L-NAME was further confirmed by the inhibition of mRNA expression for procollagen-alpha1 type III of the lung. With these results, NO produced from AM and alveolar epithelial cells after irradiation may be an important mediator in the progression of radiation pneumonitis.
Nozaki
Y
Y
First Department of Internal Medicine, Nagoya University School of Medicine, Showa-ku, Japan.
Hasegawa
Y
Y
Takeuchi
A
A
Fan
Z H
ZH
Isobe
K I
KI
Nakashima
I
I
Shimokata
K
K
D000818:Animals; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018836:Inflammation Mediators / Q000502:physiology*; D008168:Lung / Q000201:enzymology / Q000528:radiation effects; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000378:metabolism; D011347:Procollagen / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D017564:Radiation Pneumonitis / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D009573:Nitrites; D011347:Procollagen; D012333:RNA, Messenger; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester