Lw. Chen et al., Inhibition of inducible nitric oxide synthase (iNOS) prevents lung neutrophil deposition and damage in burned rats, SHOCK, 15(2), 2001, pp. 151-156
Citations number
34
Categorie Soggetti
Aneshtesia & Intensive Care","Cardiovascular & Hematology Research
This study was designed to investigate the role of NO and effect of iNOS in
hibitor on the lung neutrophil deposition and damage after burn. In Experim
ent 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 bur
n, 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 qu
antitated by measuring the extravasation of Evans blue dye (EBD). In Experi
ment 2, S-methylisothiourea (SMT) was given (7.5 mg/kg, intraperitoneal imm
ediately 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,
NOS expression were evaluated. Lung MPO activity increased up to a maxim um
of 2-fold 8th h after burn. Blood DHR 123 oxidation increased up to a maxi
mum of a 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%, respe
ctively. SMT markedly decreased the thermal injury-induced perivascular aci
d interstitial inflammatory cell infiltration and iNOS staining in bronchio
lar epithelium, endothelial cells, and perivascular and interstitial inflam
matory cells. In conclusion, thermal injury induces blood DHR 123 oxidation
, lung neutrophil deposition, lung iNOS expression, and lung damage. Peroxy
nitrite might play an important role in thermal injury-induced lung neutrop
hil 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.