NITRIC-OXIDE COUNTERACTS 5-HYDROXYTRYPTAMINE-INDUCED AND CHOLERA-TOXIN-INDUCED FLUID SECRETION AND ENHANCES THE EFFECT OF ORAL REHYDRATION SOLUTION

The effects of pharmacological modulation of the nitric oxide (NO) pat hway on intestinal fluid transport were studied in a model of ligated jejunal loops of anaesthetized rats in vivo. Close intraarterial infus ion of 5-hydroxytryptamine (5-HT) (0.16 mu g/min) induced net fluid se cretion. Intravenous infusion of the NO synthase inhibitor N-omega-nit ro-L-arginine methyl ester (L-NAME) (0.55 mg/kg per min) reversed net fluid absorption in controls to net secretion and significantly enhanc ed 5-HT-induced fluid secretion. 5-HT-induced net fluid secretion was inhibited by intravenous infusion of L-arginine (8.88 mg/kg per min), sodium nitroprusside (22.2 mu g/kg per min), or 3-morpholino sydnonimi ne (SIN-1) (22.2 mu g/kg per min). Intraluminal instillation of choler a toxin (0.5 mu g/ml) induced net secretion, which was significantly e nhanced by L-NAME and reduced by L-arginine. Another series of experim ents was performed using a model of luminally perfused jejunal loops. Cholera toxin (10 mu g/ml) induced profuse net fluid secretion also in this model. L-arginine and sodium nitroprusside significantly enhance d net fluid absorption compared to controls and abolished the secretor y effect of cholera toxin. Luminal perfusion with oral rehydration sol ution enhanced net absorption of fluid in controls and reversed choler a toxin-induced secretion to absorption. Intravenous infusion, but not intraluminal administration, of L-arginine significantly enhanced the antisecretory effect of oral rehydration solution. These results give further support to the existence of an intestinal NO-mediated proabso rptive tone. which also downregulates fluid secretion elicited by diff erent enterotoxins or mediators of secretion. Intravenous administrati on of exogenous sources of NO counteracts intestinal fluid accumulatio n and augments the antisecretory effect of oral rehydration solution, findings which may lead to therapeutic consequences.