INFLUENCE OF THE L-ARGININE NITRIC-OXIDE PATHWAY ON VASOACTIVE INTESTINAL POLYPEPTIDE RELEASE AND MOTILITY IN THE RAT STOMACH IN-VITRO

Endogenous nitric oxide (NO) plays an important role as non-adrenergic , non-cholinergic inhibitory transmitter in the gastrointestinal tract , especially in sphincter regions. The aim of this study was to invest igate the influence of NO on pyloric motility and on the release of va soactive intestinal polypeptide (VIP) in the isolated perfused rat sto mach in vitro. Therefore, pyloric motility was continously recorded by a special sleeve manometry catheter placed in the pyloric region and the concentration of VIP was determined in the venous effluent of the portal vein. Arterial perfusion with the nitrate agonist sodiumnitropr usside led to a dose-dependent reduction of the pyloric motility index (basal 166 +/- 48 mm Hg/min; sodiumnitroprusside 10(-6) M 30 +/- 20 mm Hg/min; sodiumnitroprusside 10(-4) M 0; n = 8, P < 0.001) while VIP re lease was not influenced significantly. Inhibition of endogenous NO pr oduction by the NO-synthase inhibitor N-G-nitro-L-Arg (L-NNA) signific antly increased pyloric motility (basal motility index 175 +/- 28 mmHg /min; L-NNA 10(-4) M 348 +/- 48mmHg/min; n = 8, P < 0.05). This effect was completely blocked by addition of L-Arg 10(-3) M (125 +/- 45 mm H g/min; n = 8, P < 0.01). L-NNA and L-Arg both did not influence VIP re lease. Stimulation of the vagal nerve (VS; 20 V, 20 Hz, 1 ms) led to a significant decrease of the pyloric motility index (basal 181 +/- 15 mmHg/min; VS 143 +/- 21 mmHg/min; n = 7, P < 0.05), which was consiste nt even after addition of L-NNA 10(-4) M (basal 338 +/- 58 mmHg/min; V S 228 +/- 30 mmHg/min; n = 7, P < 0.05). Vagal stimulation increased V IP release significantly (basal 14.9 +/- 1.4 pmol/l, VS 20.1 +/- 2.6 p mol/l; n = 7, P < 0.05) while L-NNA had no influence on vagally induce d VIP release. From these data, we conclude that the pylorus of the ra t is under a tonic inhibition by endogenously released NO. Under the c onditions studied, NO seems not to mediate the inhibitory effect of va gal stimulation exclusively and there seems to be no interaction betwe en NO and VIP in the rat pylorus.