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 transp ort, mucosal cyclic GMP and cyclic AMP levels and intraluminal prostag landin E(2) (PGE(2))-release were studied in a model of ligated jejuna l loops of anaesthetized rats in vivo. Experiments were performed unde r basal conditions as well as under conditions, when net fluid secreti on was induced by Escherichia coli heat stable enterotoxin a (E. coli STa) or PGE(2). 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, whe reas infusion of D-NAME, the inactive enantiomer of L-NAME, in corresp onding doses did not influence net fluid transport. N-omega-nitro-L-ar ginine (L-NOARG, 25 mg kg(-1)), another NO-synthase inhibitor, also el icited net secretion of fluid. 3 L-NAME (25 mg kg(-1))-induced net flu id 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. adminis tration of indomethacin (10 mg kg(-1)). Hexamethonium (1 mg kg(-1), s. c.), a ganglionic blocker and granisetron (100 mug kg(-1), s.c.), a 5- HT3-receptor antagonist, did not influence L-NAME-induced net secretio n. 4 Net fluid secretion induced by intraluminal instillation of E. co li 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 s odium nitroprusside (1 mg kg(-1)). D-Arginine (400 mg kg(-1)) did not influence E. coli STa-induced fluid secretion. Likewise, net fluid sec retion induced by i.a. infusion of PGE(2) (79 ng ml(-1), 30 min) was e nhanced by infusion of L-NAME and was inhibited by L-arginine and sodi um nitroprusside. D-Arginine (400 mg kg(-1)) did not influence PGE(2)- induced fluid secretion. 5 PGE(2) levels in intraluminal fluid were no t elevated after infusion of L-NAME (25 mg kg(-1)) compared to control s. 6 Mucosal cyclic GMP and cyclic AMP levels after L-NAME-treatment w ere not different from control values. 7 These results indicate that n itric oxide plays an important role in the regulation of intestinal fl uid transport. The data suggest a nitric oxide-dependent proabsorptive tone in the intestine, which possibly involves the enteric nervous sy stem and suppression of prostaglandin formation. This proabsorptive to ne also may downregulate fluid secretion induced by E. coil STa or PGE (2).