ACUTE EFFECT OF ENDOTHELIN-1 ON LUNG EDEMA INDUCED BY ALPHA-NAPHTHYLTHIOUREA (ANTU)

Alpha-naphthylthiourea when injected intraperitoneally to rats (10 mg kg(-1) i.p.) produced lung oedema as indicated by an increase in lung weight/body ratio and pleural effusion reaching a maximum within 4 hou rs. Prior intravenous single bolus injection of endothelin-1 elicited a significant and dose-dependent inhibition in both parameters. Howeve r, prior i.v. injection of angiotensin II using relatively higher dose s did not alter the oedema-producing effect of alpha-naphthylthiourea indicating a characteristic for endothelin-l. The inhibitory effect of endothelin-1 on pleural effusion is more prominent than lung weight/b ody weight ratio. The resolution of lung oedema by single bolus i.v. i njection of endothelin-1 is probably due to the acute long-lasting and potent vasoconstrictor effect of the peptide and its large accumulati on in lung tissue. Phosphoramidon, an inhibitor of endothelin converti ng enzyme, did not alter the oedema producing effect of alpha-naphthyl thiourea indicating the lack of the participation of endothelin-peptid e cascade to this pathological event. Bosentan, a non-selective recept or blocker of endothelin-1, did not inhibit the preventive effect of t he peptide against alpha-naphthylthiourea-induced lung oedema. Possibl e mechanisms of the acute effect of endothelin-1 on lung oedema are di scussed. (C) 1996 The Italian Pharmacological Society