Nitric oxide involvement in sodium choleate-induced fluid secretion and diarrhoea in rats

• Published in: European journal of pharmacology Vol. 264; no. 1; pp. 21 - 26
• Main Authors: Mascolo, Nicola, Gaginella, Timothy S., Izzo, Angelo A., Di Carlo, Giulia, Capasso, Francesco
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 13.10.1994
• Subjects: Amino Acid Oxidoreductases - antagonists & inhibitors; Amino Acid Oxidoreductases - metabolism; Animals; Arginine - analogs & derivatives; Arginine - pharmacology; Cholic Acid; Cholic Acids - antagonists & inhibitors; Cholic Acids - toxicity; Dexamethasone - pharmacology; Diarrhea; Diarrhea - chemically induced; Diarrhea - physiopathology; Epithelium - metabolism; Gastrointestinal Transit - drug effects; Intestinal secretion; Intestinal Secretions - drug effects; Intestinal Secretions - physiology; Intestine, Small - metabolism; Male; Muscle, Smooth - metabolism; NG-Nitroarginine Methyl Ester; Nitric oxide (NO) synthase; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - physiology; Nitric Oxide Synthase; Rats; Rats, Wistar; Small intestinal transit; Sodium choleate; Water-Electrolyte Balance - drug effects; Diarrhea; Intestinal secretion; Small intestinal transit; Nitric oxide (NO) synthase; Sodium choleate
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/0014-2999(94)90630-0

Bile salt-induced diarrhoea, net water and electrolyte secretion, gastrointestinal transit and nitric oxide (NO) synthase activity were studied in rats. N G - Nitro- L-arginine methyl ester (2.5–25 mg/kg i.p.), an inhibitor of NO synthase, and dexamethasone (0.03–0.3 mg/kg i.p.), an inhibitor of the inducible isoform of NO synthase, antagonized the diarrhoeal response. The NO precursor, L-arginine and isosorbide-5-mononitrate (an NO donor), reversed the inhibitory effect of N G - nitro- L-arginine methyl ester. The bile salt-stimulated fluid secretion, transit through the gut and NO synthase all were inhibited by N G - nitro- L-arginine methyl ester (but not N G - nitro- D-arginine methyl ester). NO synthase activity also was inhibited by dexamethasone. The results are consistent with bile salt induction of epithelial cell injury and concomitant synthesis of NO, mainly through activation of the inducible form of the enzyme. We believe that in this study NO is a mediator of intestinal secretion and motility changes that enhance transit of luminal contents through the gut, resulting in diarrhoea.