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Abstract
Castor oil (2 ml/rat) produced copious diarrhoea in all rats 3 h after challenge, which was associated with histologic damage to the duodenal and jejunal mucosa. Pretreatment of animals with the nitric oxide (NO) synthesis inhibitor N G -nitro-L-arginine methyl ester (L-NAME, 50 mg/kg, i.p.) reverted the diarrhoea, but, exacerbated histological damage. The NO donating compound isosorbide-5-mononitrate (IMN, 150 mg/kg p.o.) counteracted the augmentation by L-NAME of the castor oil-induced diarrhoea and histological damage. The independence of the diarrhoeal and damaging effects of castor oil suggest that NO (i) has protective effects on the rat intestinal mucosa, (ii) mediates laxation and (iii) modulates the release of local cytotoxic substances.