Inhibitors of nitric oxide synthetase prevent castor‐oil‐induced diarrhoea in the rat

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Abstract
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 NG-nitro-l-arginine methyl ester (l-NAME, 1–25 mg kg−1) and NG-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.