An unexpected interaction between NG-nitro-L-arginine methyl ester and L-arginine in alpha-naphthylthiourea-induced pulmonary oedema in rats.

This study was designed to investigate the possible participation of the L-arginine-nitric oxide (NO) pathway in the lung oedema induced by alpha-naphthylthiourea, which is a well-known noxious chemical agent in the lung. Lung oedema was assessed by measuring fluid accumulation in the pleural cavity and the lung weight/body weight ratio following alpha-naphthylthiourea injection. Administration of NG-nitro-L-arginine methyl ester, a NO synthase inhibitor, prior to alpha-naphthylthiourea, produced a significant inhibition of pleural effusion and lung weight/body weight ratio in a dose-dependent manner. L-Arginine, but not D-arginine, when used higher doses (above 300 mg/kg) prior to alpha-naphthylthiourea injection caused a significant inhibition of pleural effusion without altering lung weight/body weight ratio. Lower doses of L-arginine (below 100 mg/kg) did not elicit an inhibitory effect against alpha-naphthylthiourea-induced pulmonary damage. However, lower doses of L-arginine greatly potentiated the inhibitory effect of NG-nitro-L-arginine-methyl ester against alpha-naphthylthiourea-induced lung oedema when used in combination. The interesting aspect of this study is the inhibition by NG-nitro-L-arginine methyl ester, a NO synthase inhibitor, and L-arginine, an endogenous donor of NO, of the lung oedema induced by alpha-naphthylthiourea. The possible role of the L-arginine-NO pathway in lung oedema induced by alpha-naphthylthiourea and the possible underlying mechanisms are discussed.