Nitric oxide and castor oil-induced diarrhea

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 268; no. 1; p. 291
• Main Authors: Mascolo, N, Izzo, A A, Autore, G, Barbato, F, Capasso, F
• Format: Journal Article
• Language: English
• Published: United States 01-01-1994
• Subjects: Animals; Arginine - analogs & derivatives; Arginine - therapeutic use; Body Fluids; Castor Oil - pharmacology; Diarrhea - chemically induced; Diarrhea - prevention & control; Electrolytes - metabolism; Gastrointestinal Motility - drug effects; Intestine, Small - drug effects; Intestine, Small - physiology; Intestine, Small - secretion; Isosorbide Dinitrate - analogs & derivatives; Isosorbide Dinitrate - pharmacology; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide - physiology; Rats; Rats, Wistar
• ISSN: 0022-3565

The effect of NG-nitro-L-arginine methyl ester (L-NAME) on castor oil-induced diarrhea was studied in control rats and those treated with isosorbide dinitrate or isosorbide-5-mononitrate. Castor oil (2 ml) produced diarrhea that lasted at least 8 h. Pretreatment of the rats with L-NAME (1-25 mg/kg i.p.) 15 min before castor oil did not block the castor oil-induced diarrhea beyond 3 h after challenge but delayed its appearance (P < .05-.001). However, diarrhea was inhibited (P < .01-.001) during the entire 8 h if rats were treated twice with L-NAME (25 mg/kg) (15 min before and 3 h after castor oil). These findings suggest that L-NAME, once administered, loses its activity 3 h after its administration. The nitric oxide synthase substrate, L-arginine (150-600 mg/kg), reversed (P < .05-.01) the inhibitory effect of L-NAME on diarrhea induced by castor oil. This effect is enantiomer-specific because D-arginine (900 mg/kg) was without an effect. These results suggest that castor oil-induced diarrhea in rats involves the L-arginine nitric oxide pathway. This is further supported by the effect of isosorbide dinitrate (0.6-120 mg/kg) and isosorbide-5-mononitrate (0.6-120 mg/kg). When administered to castor oil-treated rats, these two nitric oxide-generating agents prevented in a dose-dependent fashion (P < .01-.001) the inhibitory effect of L-NAME (25 mg/kg).