vasoactive-intestinal-peptide and Intestinal-Obstruction

1. Vasoactive intestinal polypeptide (VIP) is an inhibitory neurotransmitter in the enteric nervous system. We investigated the role of VIP1/PACAP receptors in postoperative ileus in rats. 2. Different degrees of inhibition of the gastrointestinal transit, measured by the migration of Evans blue, were achieved by skin incision, laparotomy or laparotomy plus mechanical stimulation of the gut. 3. The transit after skin incision or laparotomy was not altered by the VIP1/PACAP receptor antagonist Ac-His1,D-Phe2, K15, R16, VIP(3-7), GRF(8-27)-NH2 nor by the VIP1/PACAP receptor agonist K15, R16, VIP(1-7), GRF(8-27)-NH2 and the VIP2/PACAP receptor agonist RO 25-1553 (5 microg kg(-1)). 4. However, the transit after laparotomy plus mechanical stimulation was significantly enhanced by the VIP1/PACAP receptor antagonist, whereas it was further inhibited by the VIP1/PACAP receptor agonist. The combination of the VIP1/PACAP receptor agonist and antagonist counteracted the effect of both drugs alone. The VIP2/PACAP receptor agonist did not alter the effect of the VIP1/PACAP receptor antagonist. 5. The combination of the VIP1/PACAP receptor antagonist plus the nitric oxide (NO) synthase inhibitor L-nitroarginine had no effect on the transit after laparotomy plus mechanical stimulation, while the transit after skin incision was significantly decreased. 6. These findings suggest the involvement of VIP1/PACAP receptors, next to NO, in the pathogenesis of postoperative ileus. However, the combination of the VIP1/PACAP antagonist and the NO synthase inhibitor abolished the beneficial effect of each drug alone, suggesting the need for one of the inhibitory neurotransmitters to enable normal gastrointestinal transit.

Topics: Animals; Dose-Response Relationship, Drug; Gastrointestinal Transit; Intestinal Obstruction; Male; Nitric Oxide; Postoperative Complications; Rats; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Pituitary Hormone; Receptors, Vasoactive Intestinal Peptide; Receptors, Vasoactive Intestinal Polypeptide, Type I; Vasoactive Intestinal Peptide

The neuropeptides substance P, vasoactive intestinal polypeptide, and the recently discovered peptide secretoneurin are neurotransmitters of the intrinsic nervous system of the gut and effect gut motility. The aim of this study was to investigate whether these neuropeptides are involved in the pathophysiology of large bowel ileus. Five patients underwent colonic resections for obstructive cancer of the colon. Full-thickness specimens of the resected colon were taken 10 cm proximal and 10 cm distal to the site of tumor obstruction. Substance P-, vasoactive intestinal polypeptide-, and secretoneurin-like immunoreactivities were measured in the specimens by radioimmunoassay. In addition immunocytochemistry was performed. Tissue levels of substance P, vasoactive intestinal polypeptide, and secretoneurin were lower in the prestenotic than in the poststenotic bowel segment. In accordance, immunocytochemistry revealed a denser staining of ganglion cells and fibers for all three neuropeptides in the poststenotic bowel. The decreased tissue levels of substance P, vasoactive intestinal polypeptide, and secretoneurin in the prestenotic bowel segment may contribute to the final decompensation of obstructive ileus.

Topics: Aged; Colon; Colonic Diseases; Colonic Neoplasms; Enteric Nervous System; Female; Humans; Intestinal Obstruction; Neuropeptides; Secretogranin II; Substance P; Vasoactive Intestinal Peptide

Octreotide, a somatostatin analogue that inhibits the release of most gut peptides, hastens the resolution of experimental postoperative ileus, suggesting that gut peptides mediate this process. We studied the role of two gut peptides involved in the control of normal gut motility, vasoactive intestinal peptide (VIP), and substance P (SP), in the initiation and maintenance of postoperative small bowel ileus in rats by preoperative administration of VIP and SP receptor antagonists, (VIP-ra and SP-ra). Thirty male Sprague-Dawley rats (300-350 g) underwent laparotomy. One half underwent placement of a duodenal catheter for transit studies while the other half had serosal electrodes placed on the proximal jejunum for myoelectric recordings. Six days later, animals were separated into three treatment groups of five each. Control animals were pretreated with ip saline, while the others received either VIP-ra or SP-ra prior to standardized laparotomy. Following abdominal closure, [Na51]CrO4 was injected into the duodenum and the animals were sacrificed 25 min later. The small bowel was then excised and divided into 10 equal segments. Small bowel transit was calculated as the geometric center of [Na51]CrO4 distribution. The interval until the return of migrating myoelectric complexes (MMCs) was determined in animals with intestinal electrodes. VIP-ra-treated rats demonstrated a 67% improvement in the geometric center of radiolabel relative to controls and SP-ra-treated rats had a 23% improvement (3.67 +/- 0.06 VIP-ra vs 2.69 +/- 0.09 SP-ra vs 2.20 +/- 0.09 control, P < 0.01). MMCs returned 180 +/- 17 min in controls vs 99 +/- 14 min in VIP-ra-treated rats (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Intestinal Obstruction; Male; Myoelectric Complex, Migrating; Neurokinin-1 Receptor Antagonists; Postoperative Complications; Rats; Rats, Sprague-Dawley; Receptors, Vasoactive Intestinal Peptide; Substance P; Vasoactive Intestinal Peptide

Previous observations have shown vasoactive intestinal peptide (VIP) to be an important secretagogue in the gut, whereas somatostatin has been reported to inhibit VIP release and fluid secretion.. The possible role of VIP as mediator of the inflammation and fluid losses in obstructive ileus was investigated in vivo and in a chronic rat model with thread ligation of the jejunum. Extravasated Evans blue (Eb)-stained albumin was quantified by spectrophotometry. Net fluid secretion was measured by a gravimetric technique. VIP antiserum was used to inhibit the effects of endogenous VIP. A somatostatin analogue, octreotide, was used to inhibit the release of VIP.. Results showed a pronounced plasma Eb-albumin extravasation in the wall of the obstructed gut, which was significantly inhibited by VIP antiserum (p < 0.05) or octreotide (p < 0.01). Obstruction of the jejunum resulted in net fluid secretion that was significantly reduced by administration of octreotide (p < 0.01) or VIP antiserum (p < 0.05). Net fluid secretion in control animals remained constant.. These findings suggest that VIP is an important mediator of the pathophysiology in mechanical intestinal obstruction and that somatostatin may be involved in the endogenous control of fluid losses.

Topics: Animals; Immune Sera; Intestinal Obstruction; Jejunal Diseases; Male; Octreotide; Rats; Rats, Sprague-Dawley; Somatostatin; Vasoactive Intestinal Peptide; Water-Electrolyte Imbalance

The hypothesis was that postoperative ileus might be caused by a disturbed balance between the motor-stimulating hormones, motilin and substance P, and the motor-inhibitory hormone, vasoactive intestinal polypeptide, and that octreotide might prevent this disturbance and so ameliorate the ileus. In 15 conscious dogs with chronic gastrointestinal electrodes, electrical activity was recorded and blood was drawn for radioimmunoassay of motilin, substance P, and vasoactive intestinal peptide (VIP) during fasting and after a liquid meal. Ileus was then induced by celiotomy and intestinal abrasion. During and after operation, five dogs received 154 mM NaCl only, five dogs octreotide, 0.19 micrograms/kg/hr, and five octreotide, 0.83 micrograms/kg/hr. Plasma levels of motilin, substance P, and VIP were changed little by operation, but cyclical increases in plasma motilin, which occurred preoperatively during phase III of the interdigestive myoelectric complex, were completely abolished postoperatively during ileus, as was the complex itself. Octreotide ameliorated the ileus and restored the cyclic increases in motilin found in health, nor did it alter plasma substance P and VIP. In conclusion, octreotide ameliorates postoperative ileus, but it does not do so by increasing plasma motilin or substance P or decreasing plasma VIP.

Topics: Animals; Dogs; Eating; Female; Intestinal Obstruction; Motilin; Octreotide; Postoperative Complications; Substance P; Vasoactive Intestinal Peptide

The role of vasoactive intestinal polypeptide (VIP) in small intestine obstructed rabbits and the therapeutic mechanism of Da Cheng Qi Decoction (DCQD) were studied. VIP concentrations of both blood and intestinal tissue were measured by specific radio-immunoassay in a rabbits' mechanical small intestinal obstruction model using fix of ileum to the right low abdominal wall, the influences of duodenal perfusion of DCQD on VIP levels were also investigated. 24 hours after ligating ileum, VIP of arterial plasma was elevated 7 fold, reaching 138.65 +/- 25.58 pmol/L, that of portal vein plasma was 4 times of the arterial value. VIP immunoactivity was detected in peritoneal fluid. VIP content of duodenal tissue in 16 intestine obstructed rabbits was 2 times high as that in 15 controls, whereas that of colonal tissue was inversed. DCQD caused a 50% decrease of elevated plasma VIP in experimental animals and a 65% increase in controls. The present work demonstrates that VIP might be released into the portal and peripheral circulation and mediate local and systemic pathophysiologic alterations accompanying small intestinal obstruction, such as hyperemia and edema of intestinal wall, accumulation of fluid in the lumen. VIP changes might account for the redistribution of blood flow in the obstructed segment of small intestine and the distal site of obstruction. DCQD has a therapeutic effect. The mechanism of dual modulate action of DCQD on VIP concentration is beyond our knowledge.

Topics: Animals; Drugs, Chinese Herbal; Intestinal Obstruction; Intestine, Small; Male; Rabbits; Vasoactive Intestinal Peptide

We hypothesized that bioactive peptides might be released into the portal circulation and mediate pathophysiologic alterations accompanying small bowel obstruction. We studied this question in a subacute canine small bowel obstruction model using 50 percent diameter occlusion. Control animals underwent sham laparotomy. Vasoactive intestinal peptide (VIP), peptide YY, and gastrin were measured in portal and systemic plasma by specific radioimmunoassays at 24-hour intervals as the obstruction progressed to completion over 5 days. All peptides in both groups demonstrated portal and peripheral gradients. In control dogs, peptide concentrations did not change postoperatively but VIP increased markedly in obstructed dogs, demonstrating a median portal level of 95 pmol/liter at 96 hours compared with 31.5 pmol/liter in control animals. These portal VIP levels are known to cause hypersecretion and splanchnic vasodilation in experimental models. The release of vasoactive compounds such as VIP may mediate local pathophysiology in human small bowel obstruction. A similar explanation of the systemic effects is consistent with the known cardiopulmonary bioactivity of VIP.

Topics: Animals; Dogs; Gastrins; Intestinal Obstruction; Intestine, Small; Peptide YY; Peptides; Rats; Time Factors; Vasoactive Intestinal Peptide

Topics: Child, Preschool; Colon; Colonic Neoplasms; Ganglioneuroma; Gastrointestinal Hormones; Gastrointestinal Motility; Humans; Infant; Infant, Newborn; Intestinal Obstruction; Megacolon; Vasoactive Intestinal Peptide