Nitric oxide and castor oil-induced diarrhea.
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).
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Department of Experimental Pharmacology, University of Naples Federico II, Italy.
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D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000627:therapeutic use; D001826:Body Fluids; D002368:Castor Oil / Q000494:pharmacology*; D003967:Diarrhea / Q000139:chemically induced / Q000517:prevention & control; D004573:Electrolytes / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D004573:Electrolytes; D009569:Nitric Oxide; D002368:Castor Oil; D001120:Arginine; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate; D019331:NG-Nitroarginine Methyl Ester