vasoactive-intestinal-peptide and Pyloric-Stenosis

This study aimed to quantify the neural changes in congenital pyloric stenosis in dogs and to study the comparative anatomy between this condition in dogs and that in infantile hypertrophic pyloric stenosis. Eight specimens from the pylorus of dogs with pyloric stenosis and six control specimens were examined using conventional histology and immunohistochemistry for a range of neural antigens. The changes in the proportion of nerves immunoreactive for each antigen were quantified and analysed statistically. The morphology of the nerves in the diseased dogs was similar to that in controls. Only vasoactive intestinal peptide was reduced in expression in dogs (median proportion in control dogs 0.57, in diseased dogs 0.17; P = 0.065). This study demonstrates both morphological similarities and significant differences between closely related conditions in dogs, humans and other species.

Topics: Animals; Antigens; Disease Models, Animal; Dogs; Female; Humans; Immunohistochemistry; Male; Nerve Fibers; Pyloric Stenosis; Pylorus; Vasoactive Intestinal Peptide

Infantile hypertrophic pyloric stenosis is the most common cause for urgent abdominal surgery in infancy. The aetiology of the condition is unknown. The ontogeny of the innervation and structure of the normal infant pylorus is unknown. A variety of differing histological features have been attributed to this condition and a number of animal models have been described. The histological changes in the human condition and those in the animal models have not been quantified and statistically verified. Thus, precise comparisons cannot be made. Immunohistochemistry was the principal technique employed in this study. Using this technique, the ontogeny and structure of the normal infant pylorus have been documented. The morphological and immunohistochemical changes underlying infantile hypertrophic pyloric stenosis have been quantified for the first time and compared with the quantified changes in natural and experimental animal models of this condition.

Topics: Animals; Disease Models, Animal; Dogs; Embryonic and Fetal Development; Female; Humans; Hypertrophy; Infant; Infant, Newborn; Male; Mice; Nitric Oxide Synthase; Pyloric Stenosis; Pylorus; Vasoactive Intestinal Peptide

The relaxation mechanism of the pyloric smooth muscle is largely dependent on a nonadrenergic noncholinergic (NANC) inhibitory innervation mediated in part by nitric oxide (NO). The aim of the present study was to investigate the effect of NO antagonists on the contractility of the pyloric smooth muscle. In the clinical trial, 10 anesthetized experimental rabbits were infused intraarterially with the NO synthesis inhibitor N-nitro-L-arginine (L-NNA), at a concentration of 10(-4) mol/L; 10 controls received normal saline intraarterially. Pyloric contractility was assessed by balloon manometry. L-NNA infusion produced a dose-dependent increase in the frequency of the pyloric contraction. The maximal increase in frequency occurred during the slow L-NNA infusion rate of 146 ng/min (baseline-adjusted frequencies of experimental v control: 1.267 +/- 0.389 v 0.632 +/- 0.375; P = .001). The increased frequency level was sustained over the subsequent fast infusion rate of 292 ng/min (experimental v control: 1.362 +/- 0.604 v 0.704 +/- 0.579; P = .022). Both the duration and the amplitude of the pyloric contractions were not affected by the L-NNA infusion. These findings suggest that blockage of the L-arginine-NO pathway may have resulted in inhibition of the NANC-induced gastric muscle and relaxation of the pyloric sphincter. The authors speculate that the decreased NO production may be responsible for the sustained contraction of the pyloric smooth muscle with secondary hypertrophy, characteristic of hypertrophic pyloric stenosis.

Topics: Analysis of Variance; Animals; Enzyme Inhibitors; Female; Hypertrophy; Male; Manometry; Muscle Contraction; Muscle Hypertonia; Nitric Oxide; Nitroarginine; Pyloric Stenosis; Pylorus; Rabbits; Statistics, Nonparametric; Vasoactive Intestinal Peptide

Pyloric stenosis (PS) is a common condition in infancy, which is associated with smooth muscle hypertrophy that results in pyloric outlet obstruction. The author examines the ontogeny of the peptide innervation of the pylorus in fetal tissues and an experimental model in mice and evaluates the histochemical and morphological changes in the pylorus. The data suggest that PS is an intrauterine lesion that occurs by 12 weeks' gestation. This is associated with diminished nitric oxide in human tissues and reduced enzyme activity (resulting from a deficiency in an enzyme cofactor) in mice. Increased vasoactive intestinal polypeptide expression in pyloric myenteric ganglia may be an intrinsic mechanism for resolving this condition.

Topics: Animals; Biopterins; Female; Gestational Age; Humans; Hypertrophy; Infant; Infant, Newborn; Male; Mice; Mice, Inbred Strains; Myenteric Plexus; Nitric Oxide; Nitric Oxide Synthase; Pregnancy; Pyloric Antrum; Pyloric Stenosis; Vagus Nerve; Vasoactive Intestinal Peptide

Dysfunction of pyloric inhibition has been implicated in the pathophysiology of hypertrophic pyloric stenosis. Normal inhibition likely is mediated by peptidergic enteric nerves and also may involve interstitial cells of Cajal (ICC). The authors used electron microscopy to qualitatively assess these structures in infants with pyloric stenosis and in normal controls. Pyloric muscle strips from five infants with hypertrophic pyloric stenosis, from three normal pediatric organ donors, and from three adults were examined. The following observations were made. (1) Muscle cells were primarily in a proliferative phase in pyloric stenosis and exhibited very few gap junctions between smooth muscle cells or ICC compared with the control specimens. (2) The circular muscle layer in pyloric stenosis was characterized by near absence of large granular vesicle-containing nerve fibers compared with the control specimens. (3) There were fewer nerve cell bodies in the myenteric plexus in pyloric stenosis, and the total number of ganglia was lower than that in control samples. (4) Interstitial cells of Cajal were almost completely absent in patients with hypertrophic pyloric stenosis, but there was a group of cells resembling ICC that was termed ICC-like cells. These cells may represent a failure or delay in the maturation process of the ICC. These findings show that there are significant structural abnormalities of the inhibitory nervous system in hypertrophic pyloric stenosis. The ontogenic origins and functional significance of these results require further investigation.

Topics: Case-Control Studies; Enteric Nervous System; Female; Humans; Hypertrophy; Infant; Infant, Newborn; Male; Microscopy, Electron; Muscle, Smooth; Myenteric Plexus; Pyloric Stenosis; Pylorus; Vasoactive Intestinal Peptide

Vasoactive intestinal peptide (VIP), which causes relaxation of gastrointestinal smooth muscle, has been found in high concentrations in the pylorus in many animal species, suggesting a prominent role for VIP in the control of pyloric sphincter function. We infused VIP into the gastric artery of 6 rabbits at rates from 12 to 1,200 ng/min and measured the intensity, duration, and frequency of spontaneous pyloric contractions with an intraluminal balloon and electromyography. VIP produced a dose-dependent reduction in the intensity (55% +/- 15% of baseline, P < .001) and the duration (29% +/- 25%, P < .001) of pyloric contraction. Maximal inhibition was observed at an infusion rate of 240 ng/min. The frequency of contractions did not decrease significantly in response to VIP infusion. Neostigmine infusion increased the intensity of pyloric contraction in a dose-dependent manner in doses of 0.10, 0.15, and 0.25 mg (140% +/- 78%, 273% +/- 76%, and 357% +/- 26% of baseline, respectively; P < .001). VIP infusion at 12 ng/min and 480 ng/min completely inhibited the increased intensity of contraction at neostigmine doses of 0.10 and 0.15 mg, respectively. Our results show that VIP decreases the intensity and the duration of pyloric contraction in a dose-dependent manner. As pyloric spasm may contribute to the pathogenesis of hypertrophic pyloric stenosis, we can postulate a role for reduced VIP-induced relaxation in the pathophysiology of hypertrophic pyloric stenosis.

Topics: Animals; Dose-Response Relationship, Drug; Hypertrophy; Muscle Contraction; Neostigmine; Pyloric Stenosis; Pylorus; Rabbits; Stimulation, Chemical; Vasoactive Intestinal Peptide

The distributions of nerve cells and fibers with immunoreactivity for the peptides enkephalin, gastrin-releasing peptide, neuropeptide Y, somatostatin, substance P, and vasoactive intestinal peptide were examined in specimens of myenteric plexus and external muscle from the pylorus of 20 infants with hypertrophic pyloric stenosis. These were compared with peptide distributions in pyloric samples from unaffected infants and adults. In the normal pylorus the circular muscle was richly supplied with fibers reactive for enkephalin, neuropeptide Y, substance P, and vasoactive intestinal peptide. In pyloric stenosis, these immunoreactive fiber bundles were either missing or less than 5% of normal. In contrast, there were reactive cell bodies and nerve fibers in the myenteric plexuses of both normal and affected specimens. In the samples from cases of stenosis, swollen nerve fibers that appeared to be in the process of degeneration were frequently encountered. It is concluded that infantile hypertrophic pyloric stenosis is associated with a loss of peptide immunoreactivity in nerve fibers in the circular muscle, although the same peptides are still revealed in fibers and in nerve cell bodies in the myenteric plexus.

Topics: Enkephalin, Leucine; Female; Gastrin-Releasing Peptide; Humans; Hypertrophy; Infant; Male; Myenteric Plexus; Nerve Fibers; Neuropeptide Y; Peptides; Pyloric Stenosis; Pylorus; Somatostatin; Substance P; Vasoactive Intestinal Peptide

The gastrointestinal tract harbors several populations of peptide containing nerve fibers. Among the gut neuropeptides are vasoactive intestinal peptide (VIP), substance P, enkephalin, and gastrin releasing peptide (GRP). We have examined specimens from five patients with pyloric stenosis and from five controls immunocytochemically with respect to the density of nerve fibers containing VIP, substance P, enkephalin, or GRP. In the control specimens VIP and enkephalin fibers were fairly numerous, whereas substance P and GRP fibers were few. In the pyloric stenosis patients the density of VIP fibers and enkephalin fibers was reduced in the smooth muscle. In the myenteric ganglia there was no such reduction. Substance P and GRP fibers were rare as in controls. The results indicate a reduction of VIP and enkephalin fibers in smooth muscle in pyloric stenosis patients and may be interpreted to support the view that an impaired neuronal function is involved in the pathophysiology of pyloric stenosis.

Topics: Enkephalins; Female; Fluorescent Antibody Technique; Gastrin-Releasing Peptide; Gastrins; Humans; Hypertrophy; Infant; Infant, Newborn; Male; Muscle, Smooth; Nerve Fibers; Peptides; Pyloric Stenosis; Substance P; Vasoactive Intestinal Peptide