Nitric oxide counteracts 5-hydroxytryptamine- and cholera toxin-induced fluid secretion and enhances the effect of oral rehydration solution.
The effects of pharmacological modulation of the nitric oxide (NO) pathway on intestinal fluid transport were studied in a model of ligated jejunal loops of anaesthetized rats in vivo. Close intraarterial infusion of 5-hydroxytryptamine (5-HT) (0.16 microg/min) induced net fluid secretion. Intravenous infusion of the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) (0.55 mg/kg per min) reversed net fluid absorption in controls to net secretion and significantly enhanced 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 microg/kg per min), or 3-morpholino sydnonimine (SIN-1) (22.2 microg/kg per min). Intraluminal instillation of cholera toxin (0.5 microg/ml) induced net secretion, which was significantly enhanced by L-NAME and reduced by L-arginine. Another series of experiments was performed using a model of luminally perfused jejunal loops. Cholera toxin (10 microg/ml) induced profuse net fluid secretion also in this model. L-Arginine and sodium nitroprusside significantly enhanced net fluid absorption compared to controls and abolished the secretory effect of cholera toxin. Luminal perfusion with oral rehydration solution enhanced net absorption of fluid in controls and reversed cholera 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 proabsorptive tone, which also downregulates fluid secretion elicited by different enterotoxins or mediators of secretion. Intravenous administration of exogenous sources of NO counteracts intestinal fluid accumulation and augments the antisecretory effect of oral rehydration solution, findings which may lead to therapeutic consequences.
Beubler
E
E
Department of Experimental and Clinical Pharmacology, Graz, Austria.
Schirgi-Degen
A
A
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001826:Body Fluids / Q000378:metabolism*; D002771:Cholera / Q000628:therapy; D002772:Cholera Toxin / Q000494:pharmacology*; D005260:Female; D005440:Fluid Therapy; D009129:Muscle Tonus / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012636:Secretory Rate / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*
D009569:Nitric Oxide; D012701:Serotonin; D002772:Cholera Toxin