TY - JOUR
T1 - Influence of the L-arginine-nitric oxide pathway on vasoactive intestinal polypeptide release and motility in the rat stomach in vitro
AU - Willis, Stefan
AU - Allescher, Hans Dieter
AU - Weigert, Norbert
AU - Schusdziarra, Volker
AU - Schumpelick, Volker
PY - 1996/11/7
Y1 - 1996/11/7
N2 - 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 sodium nitroprusside led to a dose-dependent reduction of the pyloric motility index (basal 166 ± 48 mm Hg/min; sodium nitroprusside 10-6 M 30 ± 20 mmHg/min; sodium nitroprusside 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 (L-NNA) 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 released 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.
AB - 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 sodium nitroprusside led to a dose-dependent reduction of the pyloric motility index (basal 166 ± 48 mm Hg/min; sodium nitroprusside 10-6 M 30 ± 20 mmHg/min; sodium nitroprusside 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 (L-NNA) 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 released 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.
KW - Motility
KW - NANC (non-adrenergic non-cholinergic)
KW - Nitric oxide (NO)
KW - Pylorus, rat
KW - VIP (vasoactive intestinal polypeptide)
UR - http://www.scopus.com/inward/record.url?scp=0030574236&partnerID=8YFLogxK
U2 - 10.1016/S0014-2999(96)00594-8
DO - 10.1016/S0014-2999(96)00594-8
M3 - Article
C2 - 8960865
AN - SCOPUS:0030574236
SN - 0014-2999
VL - 315
SP - 59
EP - 64
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1
ER -