POSSIBLE INVOLVEMENT OF EICOSANOIDS IN ALPHA-NAPHTHYLTHIOUREA-INDUCEDPULMONARY-EDEMA AND ALTERATION OF ANGIOTENSIN-CONVERTING ENZYME-ACTIVITY

Alpha-naphthylthiourea (ANTU) when injected intraperitoneally to rats at a dose of 10 mg/kg elicited lung oedema indicated by an increase in lung weight/body weight (LW/BW) ratio and pleural effusion. The injec tion of acetylsalicylic acid, which is a cyclo-oxygenase inhibitor, an d BW 755C, a cyclo-oxygenase and lipoxygenase inhibitor, prior to ANTU produced a significant inhibition in pleural fluid accumulation witho ut changing the LW/BW ratio. BW A4C, a selective 5-lipoxygenase inhibi tor, however, caused a highly significant inhibition in pleural effusi on and a slight but significant decrease in LW/BW ratio. Thromboxane A 2 synthetase inhibitor, UK 38485, caused a slight but significant inhi bition in pleural fluid accumulation without altering the LW/BW ratio. Iloprost, however, produced a slight but significant inhibition in th e LW/BW ratio without reducing the pleural effusion rate. A significan t decrease in angiotensin-converting enzyme (ACE) activity in the isol ated perfused lungs of ANTU-treated rats was noted. This observation w as thought to be an evidence of a functional alteration of the lung va scular endothelium. The possible role of eicosanoids in lung oedema in duced by ANTU and the related mechanisms of decreased ACE activity are discussed.