Effects of nitric oxide synthase inhibitor on acid aspiration-induced lung injury in rats.
The current study was designed to determine the effects of nitric oxide synthase (NOS) in the development of acid aspiration-induced lung injury in rats. Hydrochloric acid (HCl, 0.1 N; 2 ml/kg) or normal saline (NS, 2 ml/kg) was instilled into the lung of anesthetized, ventilated Sprague-Dawley rats. NG-monomethyl-L-arginine (L-NMMA, 20 mg kg(-1)) and a selective inducible nitric oxide synthase (iNOS) inhibitor, ONO-1714 (0.1 and 0.3 mg kg(-1)), were used to block NOS. Bronchoalveolar lavage fluid (BALF) and wet and dry measurements of lung (W/D) were obtained 5h after HCl or NS instillation. Unlike the control group, rats instilled with HCl showed significant increases in total nuclear cell counts (NCC), neutrophil counts, concentrations of albumin, tumor necrosis factor-alpha (TNF-alpha), interleukine-6 (IL-6) and nitrites/nitrates (NO(x)) in BALF. These parameters were associated with the significantly increased W/D in the HCl group compared with the NS group. ONO-1714 (0.1 mg kg(-1)) significantly prevented the increases in all these parameters. Its inhibitory effects were superior to those of L-NMMA and 0.3 mg kg(-1) of ONO-1714. NOS plays an important role in the pathogenesis of acid aspiration-induced lung injury. Furthermore, selective iNOS inhibition at the optimal dose was most effective in improving lung injury induced by acid aspiration in rats.
Jian
Ming-Yuan
MY
First Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
Koizumi
Tomonobu
T
Kubo
Keishi
K
D000578:Amidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000166:cytology; D002452:Cell Count; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015633:Extravascular Lung Water / Q000187:drug effects; D006574:Heterocyclic Compounds, 2-Ring / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006851:Hydrochloric Acid / Q000008:administration & dosage / Q000009:adverse effects; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D007564:Japan; D008168:Lung / Q000187:drug effects / Q000648:ultrastructure; D055370:Lung Injury; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D011015:Pneumonia, Aspiration / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000187:drug effects / Q000378:metabolism; D013053:Spectrophotometry / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000493:pharmacokinetics
C407360:7-chloro-3-imino-5-methyl-2-azabicyclo(4.1.0)heptane; D000578:Amidines; D004791:Enzyme Inhibitors; D006574:Heterocyclic Compounds, 2-Ring; D007375:Interleukin-1; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; D006851:Hydrochloric Acid