AN UNEXPECTED INTERACTION BETWEEN N-G-NITRO-L-ARGININE METHYL-ESTER AND L-ARGININE IN ALPHA-NAPHTHYLTHIOUREA-INDUCED PULMONARY-EDEMA IN RATS

This study was designed to investigate the possible participation of t he L-arginine-nitric oxide (NO) pathway in the lung oedema induced by alpha-naphthylthiourea, which is a well-known noxious chemical agent i n the lung. Lung oedema was assessed by measuring fluid accumulation i n the pleural cavity and the lung weight/body weight ratio following a lpha-naphthylthiourea injection. Administration of N-G-nitro-L-arginin e methyl ester, a NO synthase inhibitor, prior to alpha-naphthylthiour ea, produced a significant inhibition of pleural effusion and lung wei ght/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-na phthylthiourea injection caused a significant inhibition of pleural ef fusion without altering lung weight/body. Lower doses of L-arginine (b elow 100 mg/kg) did not elicit an inhibitory effect against alpha-naph thylthiourea-induced a pulmonary damage. However, lower doses of L-arg inine greatly potentiated the inhibitory effect of N-G-nitro-L-arginin e-methyl ester against alpha-naphthylthiourea-induced lung oedema when used in combination. The interesting aspect of this study is the inhi bition by N-G-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 path way in lung oedema induced by alpha-naphthylthiourea and the possible underlying mechanisms are discussed.