vasoactive-intestinal-peptide and Hypertrophy

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 neuropeptides and neuroendocrine cells are proven to exist in the human nasal mucosa. However, the pathophysiological and neuroimmunological roles of regulatory peptides in human nasal diseases require further investigation.. To investigate and compare the functional morphology and quantify the tissue concentration of regulatory peptides in the nasal mucosas of normal, allergic rhinitis (AR) and chronic hypertrophic rhinitis (CHR) subjects.. Human inferior turbinate mucosa specimens from 28 patients with AR, 25 patients with CHR and 15 patients without any nasal diseases were investigated. Using immunohistochemistry and radioimmunoassays, we detected the presence, distribution and concentrations of various neuropeptides (vasoactive intestinal peptides [VIP], neuropeptide Y [NPY], substance P [SP], calcitonin gene-related peptides [CGRP]) and general neuroendocrine markers (neurone-specific enolase, chromogranin A and somatostatin). Quantitative analysis of the stained fibres and cells were performed using a graphic AutoCAD program.. The presence and distribution of NPY, CGRP, and SP nerve fibres and neuroendocrine cells were similar among the three subject groups. AR subjects had significantly higher VIP and SP tissue concentrations. VIP fibres had highest density in AR subjects and these fibers predominantly innervated vessels. In CHR, VIP fibres primarily innervated glands.. VIP and SP may play an important neuroimmunological role in the pathogenesis of AR. VIP may lead to the hypertrophic changes of submucosal glands in the pathogenesis of CHR.

Topics: Calcitonin Gene-Related Peptide; Humans; Hypertrophy; Nasal Mucosa; Nerve Fibers; Neuropeptide Y; Neuropeptides; Neurosecretory Systems; Radioimmunoassay; Rhinitis; Rhinitis, Allergic, Perennial; Substance P; Turbinates; Vasoactive Intestinal Peptide

This study aims to investigate the roles of neuropeptides in the pathophysiology of human nasal diseases. By using immunohistochemistry and radioimmunoassay, we detected the presence, distribution and concentrations of the following neuropeptides in human nasal tissue: vasoactive intestinal peptides (VIP), neuropeptide Y (NPY), substance P (SP), and calcitonin gene-related peptides (CGRP). This was performed in human nasal inferior turbinate mucosa from 20 patients with allergic rhinitis, twenty-five patients with chronic hypertrophic rhinitis and 10 patients without any nasal disease conditions. The presence and distribution of NPY. CGRP and SP fibers among the three subject groups displayed no evident differences. VIP fibers were densely stained around the vessels in the allergic group. In contrast, these fibers were more prominently distributed around the submucosal glands of the chronic hypertrophic rhinitis group. The concentration of VIP and SP in human nasal inferior turbinate showed a significant increase in allergic subjects. Thus, VIP may be revelant to the hypertrophic changes of the nasal mucosa. Both SP and VIP may play significant neuroimmunological roles in the pathogenesis of allergic rhinitis.

Topics: Calcitonin Gene-Related Peptide; Humans; Hypertrophy; Nasal Mucosa; Neuropeptide Y; Nose Diseases; Respiratory Hypersensitivity; Rhinitis; Substance P; Vasoactive Intestinal Peptide

PACAP, VIP, anti-PACAP and anti-VIP antisera were injected intratesticularly. In 9-day-old hemicastrated rats PACAP or VIP decreased basal testosterone secretion. In 22-day-old hemicastrates VIP but not PACAP reduced compensatory testicular hypertrophy, however, neither PACAP nor VIP altered steroidogenesis. Anti-VIP antiserum to this age group increased testosterone production and enhanced compensatory testicular hypertrophy. In adult hemicastrates neither the peptides nor the antisera influenced steroidogenesis. Neither in immatures nor in adults treatment of both testes with PACAP or VIP had any effect. Data indicate that both PACAP and VIP might exert a local action on testicular steroidogenesis, on compensatory testicular hypertrophy, and these effects are age-dependent.

Topics: Animals; Antibodies; Hypertrophy; Male; Neuropeptides; Orchiectomy; Organ Size; Pituitary Adenylate Cyclase-Activating Polypeptide; Rats; Rats, Sprague-Dawley; Steroids; Testis; Testosterone; 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

The neuropeptides which have been immunolocalised within the adrenal cortex have a role in regulating steroidogenesis and adrenal blood flow, but little is known of the mechanisms which regulate adrenal neuropeptide content. The present studies were designed to investigate the regulation in the rat of three adrenal neuropeptides, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY) and substance P (SP), looking at the effects of splanchnic nerve section and also investigating the effects of unilateral adrenalectomy on the neuropeptide content of the contralateral adrenal following 9 days of compensatory growth. Splanchnic nerve section, followed by a 10-day recovery period, caused a significant increase in immunoreactive NPY (irNPY) and irSP content, but had no effect on irVIP in the capsular/zona glomerulosa portion of the rat adrenal gland. In the inner zone/medullary fraction, however, irVIP was significantly decreased, while irNPY and irSP were unaffected by splanchnic nerve section. Unilateral adrenalectomy had no effect on the contralateral adrenal content of any of the peptides, although the left adrenal gland increased in size by around 60% 9 days after removal of the right adrenal. These data suggest that NPY and SP in the rat adrenal capsule/zona glomerulosa and VIP in the inner zones/medulla, are regulated, directly or indirectly, by splanchnic nerve activity, but that VIP in the outer cortex, and NPY and SP in the inner zones are regulated by another mechanism, which is, at present, unclear. These data do not support a role for VIP, NPY or substance P in the adrenal hypertrophic response to unilateral adrenalectomy in the rat.

Topics: Adrenal Glands; Animals; Female; Hypertrophy; Immunoassay; Neuropeptide Y; Rats; Rats, Wistar; Splanchnic Nerves; Substance P; 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

Embryonic hypothalamic tissue originating from spontaneously hypertensive rats (SHR) was implanted in young normotensive Wistar Kyoto rats in an attempt to localize hypothalamic regions directly responsible for the induction of hypertension. A 25% increase in host systolic blood pressure as compared with the controls was recorded 3 months after implantation in the animals receiving rostral hypothalamic tissue (R-SHR), whereas blood pressure was not affected in the animals grafted with caudal hypothalamic tissue (C-SHR). The hypertension in the R-SHR group was accompanied by hypertrophy of the heart and kidneys. The number of vasopressin-immunopositive (VPi) parvocellular cells in the hypothalamic paraventricular nucleus (PVN) of the R-SHR group was massively reduced (by 72%), while that of the tyrosine hydroxylase-immunopositive cells displayed no change. In the suprachiasmatic nucleus of these animals the VPi cell number was unaltered. In the C-SHR, the amount of parvocellular VPi cells was also unaltered. Likewise, oxytocin-containing cells were the same in all groups. DNA nick-end labeling of the tissue revealed that PVN cells are undergoing programmed cell death. These results implicate a selective degeneration by hypothalamic PVN cells in the pathogenesis of hypertension.

Topics: Animals; Apoptosis; Brain Tissue Transplantation; Female; Fetal Tissue Transplantation; Hypertension; Hypertrophy; Hypothalamus; Immunoenzyme Techniques; Nerve Degeneration; Neurons; Pregnancy; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Tyrosine 3-Monooxygenase; Vasoactive Intestinal Peptide

The effects of a 7-day intraperitoneal infusion with VIP (0.03 nmol.kg-1.min-1) and its antagonist [4-Cl-D-Phe6,Leu17]-VIP (VIP-A; 3 nmol.kg-1.min-1) were studied in sham and bilaterally adrenalectomized rats bearing ACTH and angiotensin II (ANG-II)-responsive adrenocortical autotransplants. VIP significantly increased plasma aldosterone (ALDO) concentration (PAC) and lowered plasma renin activity (PRA) in both groups of animals, without affecting plasma levels of ACTH and corticosterone. This treatment caused a marked hypertrophy of adrenal zona glomerulosa (ZG) and its parenchymal cells (without inducing any significant change in the zona-fasciculata morphology), as well as of ZG-like cells of autotransplants. Isolated ZG cells and autotransplant quarters obtained from VIP-infused rats evidenced a notable increase in both their basal and maximally ACTH- or ANG-II-stimulated ALDO secretion. The simultaneous infusion of rats with VIP-A completely reversed all these effects of VIP. The infusion with VIP-A alone caused, in sham-operated rats, a net decrease in PAC, coupled with a rise in PRA, and a marked atrophy of ZG and ZG cells; basal and maximally stimulated ALDO secretion of dispersed ZG cells was also significantly lowered. Conversely, VIP-A did not evoke any appreciable effect in autotransplanted rats. These findings suggest that endogenous VIP is specifically involved in the maintenance of the growth and secretory capacity of rat adrenal ZG. Since regenerated adrenocortical autotransplants, which are responsive to VIP but not to VIP-A infusion, are completely deprived of chromaffin cells, the hypothesis is advanced that adrenal medulla may be the source of endogenous VIP regulating ZG function.

Topics: Adrenocorticotropic Hormone; Aldosterone; Angiotensin II; Animals; Blood Pressure; Corticosterone; Hypertrophy; Male; Mitochondria; Rats; Rats, Wistar; Renin; Vasoactive Intestinal Peptide; Zona Glomerulosa

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

In unanesthetized, normal rats, and rats with bladder hypertrophy following infravesical outflow obstruction, cystometry was performed to investigate the effects of spinal and peripheral administration of vasoactive intestinal polypeptide (VIP) on micturition. In addition, the direct effects of the peptide on isolated smooth muscle preparations of detrusor and urethra were studied. In normal animals, 10 micrograms. of VIP administered intrathecally as well as intra-arterially close to the bladder, but not intravenously, decreased micturition volume and bladder capacity, and facilitated spontaneous bladder contractions. In animals with bladder hypertrophy, the same dose of VIP intrathecally had similar effects on these three parameters, but the effects of VIP given intra-arterially were less pronounced. VIP given intravenously was ineffective. Hexamethonium 5 mg. x kg.-1 given intraarterially did not block the stimulatory effect of VIP 10 micrograms. given intra-arterially to normal animals. VIP had negligible effects on isolated detrusor muscle contracted by carbachol or electrical stimulation, or on urethral preparations contracted by noradrenaline. These results suggest that VIP has a facilitatory action on the micturition reflex at the spinal cord and ganglionic levels.

Topics: Animals; Female; Hypertrophy; Muscle, Smooth; Rats; Rats, Sprague-Dawley; Reflex; Synaptic Transmission; Urethra; Urinary Bladder; Urinary Bladder, Neurogenic; Urination; Vasoactive Intestinal Peptide

A typical case of megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is reported. The patient, an infant girl, was fed only by total intravenous nutrition and is now 3 years old. The distribution of several gut peptides was examined in the resected small intestine using an immunohistochemical method. Vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM)-containing nerve fibers were decreased; however, substance P- and leucine enkephalin (Leu-ENK)-containing fibers were increased. The imbalance between several kinds of gut peptides might be one the causes of aperistalsis in MMIHS. This is the first report about the gut peptides of MMIHS.

Topics: Autonomic Nervous System; Colon; Colonic Pseudo-Obstruction; Cystitis; Female; Follow-Up Studies; Humans; Hypertrophy; Infant, Newborn; Intestinal Pseudo-Obstruction; Intestine, Small; Peristalsis; Syndrome; 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