Influence of the l-arginine-nitric oxide pathway on vasoactive intestinal polypeptide release and motility in the rat stomach in vitro

Abstract

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 investigate the influence of NO on pyloric motility and on the release of vasoactive intestinal polypeptide (VIP) in the isolated perfused rat stomach 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 sodiumnitroprusside led to a dose-dependent reduction of the pyloric motility index (basal 166 ± 48 mm Hg/min; sodiumnitroprusside 10 −6 M 30 ± 20 mmHg/min; sodiumnitroprusside 10 −4 M 0; n = 8, P < 0.001) while VIP release was not influenced significantly. Inhibition of endogenous NO production by the NO-synthase inhibitor N G-nitro- l-Arg ( lNNA) significantly increased pyloric motility (basal motility index 175 ± 28 mmHg/min; l-NNA 10 −4 M 348 ± 48 mmHg/min; n = 8, P < 0.05). This effect was completely blocked by addition of l-Arg 10 −3 M (125 ± 45 mm Hg/min; n = 8, P < 0.01). l-NNA and l-Arg both did not influence VIP release. 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 consistent even after addition of l-NNA 10 −4 M (basal 338 ± 58 mmHg/min; VS 228 ± 30 mmHg/min; n = 7, P < 0.05). Vagal stimulation increased VIP release significantly (basal 14.9 ± 1.4 pmol/l; VS 20.1 ± 2.6 pmol/l; n = 7, P < 0.05) while l-NNA had no influence on vagally induced VIP release. From these data, we conclude that the pylorus of the rat is under a tonic inhibition by endogenously release NO. Under the conditions studied, NO seems not to mediate the inhibitory effect of vagal stimulation exclusively and there seems to be no interaction between NO and VIP in the rat pylorus.