Regulation of gastric mucosal integrity by endogenous nitric oxide: interactions with prostanoids and sensory neuropeptides in the rat

Abstract

1 The interactions between nitric oxide (NO), prostacyclin and sensory neuropeptides in the maintenance of gastric mucosal integrity have been investigated in the anaesthetized rat. 2 Administration of either N^G-monomethyl-l-arginine (l-NMMA) to inhibit endothelium-derived NO formation, indomethacin to inhibit prostanoid biosynthesis or chronic capsaicin pretreatment to deplete sensory neuropeptides, did not induce acute mucosal injury. 3 In capsaicin-pretreated rats, however, l-NMMA (12.5–100 mg kg⁻¹ i.v.) dose-dependently induced acute mucosal damage, characterized as vasocongestion and haemorrhagic necrosis. The enatiomer d-NMMA (100 mg kg⁻¹ i.v.) did not induce any detectable mucosal damage. 4 This mucosal injury induced by l-NMMA was inhibited by concurrent administration of l-arginine (300 mg kg-¹ i.v.). 5 In indomethacin (5 mg kg⁻¹ i.v.)-pretreated rats, l-NMMA also induced mucosal damage. Furthermore, following indomethacin administration in capsaicin-pretreated rats, l-NMMA induced widespread, severe haemorrhagic necrotic damage. 6 These findings suggest a role for endogenous NO formed from l-arginine, acting in concert with prostacyclin and sensory neuropeptides, in the modulation of gastric mucosal integrity.