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 5 h 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-α (TNF-α), interleukine-6 (IL-6) and nitrites/nitrates (NOx) 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.