Role of oxygen-derived metabolites in the rat gastric mucosal injury induced by nitric oxide donors.

Abstract Local intra-arterial infusion of high doses of the nitric oxide (NO) donor, nitroprusside (10–40 μg kg −1 min −1 for 15 min) induced dose-dependent haemorrhagic injury to the rat gastric mucosa and reduced systemic arterial blood pressure, whereas intragastric nitroprusside (10–50 mg ml −1 ), which caused similar falls in blood pressure, failed to induce such injury. The mucosal damage induced by nitroprusside was reduced by local concurrent infusion of superoxide dismutase (500–4000 i.u. kg −1 ). Local superoxide dismutase also abolished the mucosal injury induced by local infusion of the NO donor, S -nitroso- N -acetyl-penicillamine (40 μg kg −1 min −1 ), but not that induced by local infusion of endothelin-1 (5 pmol kg −1 min −1 ) indicating specific actions. Intravenous infusion of the iron chelator and peroxyl scavenger, desferrioxamine (0.25–1 mg kg −1 min −1 ) or the hydroxyl radical scavenger, dimethylthiourea (20 mg kg −1 min −1 ) also reduced the mucosal damage induced by the local administration of the NO donors, but not that induced by endothelin-1. These findings implicate the involvement of superoxide and possibly other oxygen-derived free radicals in the injurious actions of high levels of nitric oxide generated from NO donors, and may reflect a role of the cytotoxic peroxynitrite moiety.