An unexpected interaction between NG-nitro- l-arginine methyl ester and l-arginine in α-naphthylthiourea-induced pulmonary oedema in rats

• Published in: European journal of pharmacology Vol. 321; no. 1; pp. 45 - 51
• Main Authors: Sipahi (Yilmaz), Emine, Hodoğlugil, Uğur, Üstün, Hüseyin, Zengil, Hakan, Türker, R.Kazim, Ercan, Z.Sevim
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 19-02-1997; Elsevier
• Subjects: Animals; Arginine - pharmacology; Biological and medical sciences; Chemical and industrial products toxicology. Toxic occupational diseases; d-Arginine; Drug Synergism; Enzyme Inhibitors - pharmacology; Female; l-Arginine; Lung - pathology; Male; Medical sciences; NG-Nitro- l-arginine methyl ester; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide (NO); Nitric Oxide Synthase - antagonists & inhibitors; Pleural Effusion - pathology; Pulmonary Circulation - drug effects; Pulmonary Edema - chemically induced; Pulmonary Edema - pathology; Pulmonary Edema - prevention & control; Pulmonary oedema; Rats; Stereoisomerism; Thiourea - analogs & derivatives; Toxicology; Various organic compounds; α-Naphthylthiourea; N G-Nitro- l-arginine methyl ester; l-Arginine; α-Naphthylthiourea; d-Arginine; Pulmonary oedema; Nitric oxide (NO); Lung disease; Edema; Intraperitoneal administration; Rat; Respiratory disease; Toxicity; Lung; Rodentia; Thioureas; Vertebrata; Mammalia; Animal; Nitric oxide; Mechanism of action
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(96)00932-6

This study was designed to investigate the possible participation of the
l-arginine-nitric oxide (NO) pathway in the lung oedema induced by α-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 α-naphthylthiourea injection. Administration of
N
G-nitro-
m-arginine methyl ester, a NO synthase inhibitor, prior to α-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 α-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 α-naphthylthiourea-induced pulmonary damage. However, lower doses of
l-arginine greatly potentiated the inhibitory effect of
N
G-nitro-
l-arginine-methyl ester against α-naphthylthiourea-induced lung oedema when used in combination. The interesting aspect of this study is the inhibition 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 α-naphthylthiourea. The possible role of the
l-arginine-NO pathway in lung oedema induced by α-naphthylthiourea and the possible underlying mechanisms are discussed.