Significance of nitric oxide in the stimulation of intestinal fluid absorption in the rat jejunum in vivo.
1. The effects of inhibiting nitric oxide (NO)-synthase on fluid transport, mucosal cyclic GMP and cyclic AMP levels and intraluminal prostaglandin E2 (PGE2)-release were studied in a model of ligated jejunal loops of anaesthetized rats in vivo. Experiments were performed under basal conditions as well as under conditions, when net fluid secretion was induced by Escherichia coli heat stable enterotoxin a (E. coli STa) or PGE2. 2. Intravenous infusion of the NO-synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 0.25-50 mg kg-1, 45 min) dose-dependently reversed net fluid absorption to net secretion, whereas infusion of D-NAME, the inactive enantiomer of L-NAME, in corresponding doses did not influence net fluid transport. N omega-nitro-L-arginine (L-NOARG, 25 mg kg-1), another NO-synthase inhibitor, also elicited net secretion of fluid. 3. L-NAME (25 mg kg-1)-induced net fluid secretion was reversed to net absorption by infusion of L-arginine (400 mg kg-1) or sodium nitroprusside (1 mg kg-1) and s.c. administration of indomethacin (10 mg kg-1). Hexamethonium (1 mg kg-1, s.c.), a ganglionic blocker and granisetron (100 micrograms kg-1, s.c.), a 5-HT3-receptor antagonist, did not influence L-NAME-induced net secretion. 4. Net fluid secretion induced by intraluminal instillation of E. coli STa (10 units ml-1) was enhanced by infusion of L-NAME (25 mg kg-1) and was inhibited by infusion of L-arginine (400 mg kg-1) and sodium nitroprusside (1 mg kg-1). D-Arginine (400 mg kg-1) did not influence E. coli STa-induced fluid secretion. Likewise, net fluid secretion induced by i.a. infusion of PGE2 (79 ng ml-1, 30 min) was enhanced by infusion of L-NAME and was inhibited by L-arginine and sodium nitroprusside. D-Arginine(400 mg kg-1) did not influence PGE2-induced fluid secretion.5. PGE2 levels in intraluminal fluid were not elevated after infusion of L-NAME (25mgkg-1) compared to controls.6. Mucosal cyclic GMP and cyclic AMP levels after L-NAME-treatment were not different from control values.7. These results indicate that nitric oxide plays an important role in the regulation of intestinal fluid transport. The data suggest a nitric oxide-dependent proabsorptive tone in the intestine, which possibly involves the enteric nervous system and suppression of prostaglandin formation. This proabsorptive tone also may downregulate fluid secretion induced by E. coli STa or PGE2.
Schirgi-Degen
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A
Department of Experimental and Clinical Pharmacology, Karl-Franzens-University of Graz, Austria.
Beubler
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E
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007408:Intestinal Absorption / Q000187:drug effects*; D007583:Jejunum / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D009569:Nitric Oxide; D001120:Arginine; D000242:Cyclic AMP; D015232:Dinoprostone; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin