Inhibition of inducible nitric oxide synthase (iNOS) prevents lung neutrophil deposition and damage in burned rats.
This study was designed to investigate the role of NO and effect of iNOS inhibitor on the lung neutrophil deposition and damage after burn. In Experiment 1, specific pathogen-free (SPF) Sprague-Dawley rats underwent 35% total body surface area (TBSA) burn. On the 4th, 8th, 16th, and 24th h after burn, blood was collected for peroxynitrite-mediated dihydrorhodamine 123 (DHR 123) oxidation assay, and lung tissues were harvested for myeloperoxidase (MPO) test and histologic study. Pulmonary microvascular dysfunction was quantitated by measuring the extravasation of Evans blue dye (EBD). In Experiment 2, S-methylisothiourea (SMT) was given (7.5 mg/kg, intraperitoneal immediately post-burn) to suppress iNOS activity. On the 8th h after burn, the effect of SMT on blood DHR 123 oxidation, lung MPO, lung damage, and lung iNOS expression were evaluated. Lung MPO activity increased up to a maximum of 2-fold 8 h after burn. Blood DHR 123 oxidation increased up to a maximum of 2-fold 8 h after burn. Lung permeability increased up to a maximum of 2.5-fold 4 h after burn. SMT significantly decreased lung MPO activity, blood DHR 123 oxidation, and lung permeability by 31%, 41%, and 54%, respectively. SMT markedly decreased the thermal injury-induced perivascular and interstitial inflammatory cell infiltration and iNOS staining in bronchiolar epithelium, endothelial cells, and perivascular and interstitial inflammatory cells. In conclusion, thermal injury induces blood DHR 123 oxidation, lung neutrophil deposition, lung iNOS expression, and lung damage. Peroxynitrite might play an important role in thermal injury-induced lung neutrophil deposition and damage. Specific inhibition of lung iNOS expression and blood DHR 123 oxidation with SMT on thermal injury not only attenuated the lung neutrophil deposition, but also reduced lung damage.
Chen
L W
LW
Department of Surgery, Veterans General Hospital-Kaohsiung, National Yang-Ming Medical University, Taipei, Taiwan.
Hsu
C M
CM
Wang
J S
JS
Chen
H L
HL
Chen
J S
JS
D000818:Animals; D002056:Burns / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007550:Isothiuronium / Q000031:analogs & derivatives* / Q000494:pharmacology; D008168:Lung / Q000201:enzymology / Q000473:pathology; D055370:Lung Injury; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010539:Permeability; D009195:Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012235:Rhodamines / Q000097:blood
D004791:Enzyme Inhibitors; D012235:Rhodamines; D007550:Isothiuronium; D009569:Nitric Oxide; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C027744:S-methylisothiopseudouronium