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 challenge, which-was associated with gross damage to the duodenal and jejunal mucosa. 2 The injury was accompanied by release of acid phosphatase into the gut lumen, indicating cellular injury. 3 Intraperitoneal injection of the nitric oxide (NO) synthase inhibitor N-G-nitro-L-arginine methyl ester (L-NAME, 2.5-50 mg kg(-1) twice), prevented the diarrhoea. The dose of L-NAME (50 mg kg(-1)) completely blocked the diarrhoea but increased the release of acid phosphatase and worsened the gross damage. 4 The NO donating compound, isosorbide-5-mononitrate (IMN, 150 mg kg(-1) twice) reversed the effects of L-NAME (50 mg kg(-1)) on castor 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.