INHIBITORS OF NITRIC-OXIDE SYNTHETASE PREVENT CASTOR-OIL-INDUCED DIARRHEA IN THE RAT

1 Castor oil (2 ml orally) produced copious diarrhoea in rats 3 h after its administration. 2 Pretreatment (intraperitoneal, i.p.) of rats with the NO synthesis inhibitors N(G)-nitro-L-arginine methyl ester (L-NAME, 1-25 mg kg-1) and N(G)-monomethyl-L-arginine (L-NMMA, 2.5- 100 mg kg-1) inhibited or prevented castor-oil-induced diarrhoea. L-Arginine (150-600 mg kg-1, i.p.) administered to rats pretreated with L-NAME 10 mg kg-1, drastically reduced the antidiarrhoeal activity of L-NAME in a dose-related manner. D-Arginine (900 mg kg-1) did not modify the protection by L-NAME. 3 Pretreatment (i.p.) of rats with L-NAME (2.5 - 25 mg kg-1) decreased the intestinal fluid accumulation and Na+ secretion induced by castor oil. L-Arginine (600 mg kg-1) but not D-arginine (900 mg kg-1) counteracted the inhibitory effect of L-NAME (10 mg kg-1). 4 L-NAME (10 and 25 mg kg-1) had no significant effect on the intestinal transit in normal rats or those given castor oil. 5 These results provide evidence that nitric oxide (NO) could play an important role in castor-oil-induced diarrhoea.