Morphine modulates inducible nitric oxide synthase expression and reduces pulmonary oedema induced by α-naphthylthiourea

This study was designed to investigate the possible participation of morphine in pulmonary oedema induced by alpha-naphthylthiourea (ANTU), which is a well-known noxious chemical agent in the lung. Injection of ANTU (15 mg/kg i.p.) produced pulmonary oedema as indicated by an increase in lung weight/body weight ratio and pleural effusion reaching a maximum within 4 h in rat. Administration of morphine prior to ANTU significantly inhibited to pulmonary oedema with a dose-dependent manner. The protective effect of morphine is prevented by peripheral opioid receptor antagonist, naloxone methiodide. ANTU-treated rats were shown positive by inducible nitric oxide synthase immunohistochemical staining. There was no staining in the control group. On the other hand, the degree of staining was markedly reduced in tissue sections by morphine. These results suggest that previous administration of subcutaneous morphine has preventive effect on ANTU-induced pulmonary inflammatory reaction and its effect mediated via peripheral opioid receptors. Application of naloxone with ANTU has no effect on the lung parameters indicating that endogenous opioids do not modulate ANTU-induced damage. (c) 2005 Elsevier B.V. All rights reserved.