DISSOCIATION OF CASTOR OIL-INDUCED DIARRHEA AND INTESTINAL MUCOSAL INJURY IN RAT - EFFECT OF N-G-NITRO-L-ARGININE METHYL-ESTER

1 Castor oil (2 ml orally) produced diarrhoea in rats 1-7 h after chal lenge, which-was associated with gross damage to the duodenal and jeju nal mucosa. 2 The injury was accompanied by release of acid phosphatas e into the gut lumen, indicating cellular injury. 3 Intraperitoneal in jection of the nitric oxide (NO) synthase inhibitor N-G-nitro-L-argini ne methyl ester (L-NAME, 2.5-50 mg kg(-1) twice), prevented the diarrh oea. The dose of L-NAME (50 mg kg(-1)) completely blocked the diarrhoe a but increased the release of acid phosphatase and worsened the gross damage. 4 The NO donating compound, isosorbide-5-mononitrate (IMN, 15 0 mg kg(-1) twice) reversed the effects of L-NAME (50 mg kg(-1)) on ca stor oil-induced diarrhoea, gross damage and acid phosphatase release. 5 The apparent dissociation of the diarrhoeal and intestinal mucosal damaging effects of castor oil suggest that NO has a protective effect on the rat duodenal and jejunal mucosa, but that NO mediates, in part , the diarrhoea effect of this laxative.