Inhibition of nitric oxide synthase attenuates NNMU-induced alveolar injury in vivo

The purpose of this study was to determine if the acute alveolar injury induced by subcutaneous injections ofN-nitroso-N-methylurethane (NNMU) in rats is mediated by nitric oxide (NO ⋅). We show that intraperitoneal injections of the NO ⋅ synthase (NOS) inhibitor N ω-nitro-l-arginine methyl ester (l-NAME) or aminoguanidine significantly attenuate the NNMU-induced alveolar injury as assessed by 1) normalization of the alveolar-arterial O2difference, 2) attenuation of the lowered phospholipid-to-protein ratio in the crude surfactant pellet (CSP), 3) attenuation of the elevated minimal surface tension of the CSP, and4) attenuation of polymorphonuclear neutrophilic infiltration into the alveolar space. Injections ofN ω-nitro-d-arginine methyl ester, the inactive stereoisoform ofl-NAME, did not affect the acute lung injury. Western blot analysis of whole lung homogenates demonstrate an elevated expression of transcriptionally inducible, Ca2+-independent NOS (iNOS) in NNMU-injected rats compared with control sa...