vasoactive intestinal polypeptide
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The effects of transient and sustained hyperthyroidism on vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI) levels were studied in the heart atria of developing and adult rats. Newborn rats were divided into 5 groups. Neo-T animals were treated with thyroxine (T4) during postnatal days 1-8 and sacrificed at the age of 60 days. Neo-S rats were treated with T4 during postnatal days 1-60 and sacrificed one day later. Adult-1 and Adult-2 animals received T4 during days 52-60 and were sacrificed 5-6 days and 1 day later, respectively. Control animals were injected with saline. VIP-LI concentrations were determined in extracts from the left and right atria separately. In Neo-S and Adult-2 rats, spontaneous heart rate, the weight of both atria and total T4 serum levels were significantly enhanced, while their body weight was decreased. The ratio atria weight to body weight was significantly increased in all groups except for Adult-1 animals. Hyperthyroidism led to a significant decrease in VIP-LI levels in both atria of Neo-S and Neo-T rats. Hyperthyroidism induced in adult rats also decreased VIP-LI levels in both atria. However, this change was only transient. In conclusion, our data have provided new evidence that hyperthyroidism induced during the early neonatal period interferes with the development of VIP-ergic innervation in rat atria. The period of the first few postnatal days seems to be essential for this effect, since VIP-LI concentrations in 60-day-old animals did not significantly differ between Neo-S and Neo-T atria.
- MeSH
- hypertyreóza metabolismus MeSH
- krysa rodu Rattus MeSH
- potkani Wistar MeSH
- srdeční síně metabolismus MeSH
- stárnutí metabolismus MeSH
- vazoaktivní intestinální peptid metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- vazoaktivní intestinální peptid MeSH
OBJECTIVES: To determine putative effects of various protocols of propylthiouracil (PTU)-induced hypothyroidism on vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI) levels in the atria of developing and adult female rats. ANIMALS AND METHODS: Perinatal hypothyroidism was induced by treating pregnant rats with 0.05% PTU in drinking water from late gestation till the age of 60 days (P-PTU). Adult rats were given PTU for 10, 30 or 70 days (PTU-10, PTU-30 and PTU-70, respectively). Corresponding age-matched controls were left intact (P-Cont, Cont-10, Cont-30 and Cont-70, respectively). Resting heart rate, serum total thyroxine concentration, body weight and atrial weight were determined in all animals. VIP-LI levels in tissue extracts were measured by radioimmunoassay. RESULTS: The values of heart rate, serum total thyroxine, body weight and atrial weight showed that 10-day treatment did not suppress thyroid gland function completely. However, the remaining experimental protocols were sufficient to reach stable hypothyroid conditions. Thyroid hormone deficiency led to a significant increase in VIP-LI levels in both atria of PTU-30 and PTU-70 rats (P<0.01 versus corresponding controls). Interestingly, in P-PTU atria, VIP-LI reached significantly higher values than in rats treated with PTU for the same time during adulthood (PTU-70). CONCLUSIONS: These results provide new evidence that hypothyroidism interferes with VIP-ergic innervation in rat heart atria. The impact of thyroid hormone deficiency on VIP-LI levels differed in P-PTU and PTU-70 rats suggesting that thyroid hormone may play an important part in the development of VIP-ergic innervation in rat heart atria.
- Klíčová slova
- Atria, Development, Hypothyroidism, Rat, Vasoactive intestinal polypeptide,
- Publikační typ
- časopisecké články MeSH
Vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI) and calcitonin gene-related peptide (CGRP)-LI concentrations were determined in the developing rat heart atria using radioimmunoassay. Peptide levels were analysed on postnatal days 1, 10, 25, 45, 60, and 85 (P1-P85) separately in the right (RA) and left atria (LA). No sex differences were revealed at any age examined. VIP-LI has been already detected in both atria at P1 in concentrations comparable to values at P10. In the RA, VIP-LI levels increased significantly between days P10 and P25, remained high at P45 and then declined. In the LA, VIP-LI concentrations did not differ from those in the RA on days P1, P10, P25, and P45. However, regional differences were found at P60 and P85, when the peptide levels were significantly higher in the LA than in the RA. The postnatal changes in CGRP-LI concentrations were comparable in both atria with similar values at P1 and P85. After birth, CGRP levels decreased gradually till P45, then they increased till P60 and declined again at P85. The results demonstrate that there is an asymmetry in the postnatal development of the atrial VIP-LI and CGRP-LI concentrations. VIP-LI levels reached their maximum at P25, whereas CGRP-LI levels at P60. Relatively high peptide concentrations in neonatal atria and their variations during development might be related to diverse trophic functions of VIP and CGRP.
- MeSH
- autonomní nervové dráhy cytologie růst a vývoj metabolismus MeSH
- krysa rodu Rattus MeSH
- peptid spojený s genem pro kalcitonin metabolismus MeSH
- potkani Wistar MeSH
- srdeční síně cytologie růst a vývoj inervace metabolismus MeSH
- tělesná hmotnost fyziologie MeSH
- vazoaktivní intestinální peptid metabolismus MeSH
- velikost orgánu fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- peptid spojený s genem pro kalcitonin MeSH
- vazoaktivní intestinální peptid MeSH
Vasoactive intestinal polypeptide (VIP) is believed to coexist with acetylcholine in postganglionic parasympathetic neurones. However, the presence of VIP in extrinsic nerves and/or other types of intrinsic cardiac neurones has not been excluded. The aim of our study was to examine the distribution and origin of VIP-ergic innervation in the rat heart atria using immunocytochemistry and radioimmunoassay (RIA) combined with two types of denervation: sympathectomy, which was produced by guanethidine treatment and sensory denervation achieved by capsaicin administration. In whole-mount preparations of the intact atria, VIP-immunoreactive (IR) nerve fibres and ganglionic cells were found, the latter being much more numerous in the left atria (LA) than in the right ones. Some of VIP-IR nerve fibres forming bundles appeared to be extrinsic in origin. VIP-IR concentrations determined by RIA in the intact rats were significantly higher in the LA than in the right ones (p < 0.01). However, no changes in VIP-IR levels were found in either atrium after both guanethidine and capsaicin treatment protocols, thus indicating that VIP-immunoreactivity is not associated with either sympathetic or sensory innervation. In conclusion, the ganglionated plexus of the rat atria may comprise at least 3 different neuronal populations expressing VIP-positivity: 1. extrinsic preganglionic parasympathetic fibres, 2. intrinsic postganglionic parasympathetic neurones and 3. intrinsic local circuit neurones that do not express a cholinergic phenotype.
- MeSH
- cholin-O-acetyltransferasa metabolismus MeSH
- ganglia autonomní cytologie metabolismus MeSH
- guanethidin farmakologie MeSH
- imunohistochemie MeSH
- kapsaicin farmakologie MeSH
- krysa rodu Rattus MeSH
- myokard cytologie metabolismus MeSH
- nervová vlákna metabolismus ultrastruktura MeSH
- srdce účinky léků MeSH
- srdeční síně inervace MeSH
- thiolesterasa ubikvitinu MeSH
- thiolesterhydrolasy analýza MeSH
- vazoaktivní intestinální peptid metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cholin-O-acetyltransferasa MeSH
- guanethidin MeSH
- kapsaicin MeSH
- thiolesterasa ubikvitinu MeSH
- thiolesterhydrolasy MeSH
- vazoaktivní intestinální peptid MeSH
Vasoactive intestinal polypeptide (VIP) is implicated in the modulation of vagal effects on the heart rate. In this study, the impact of acute and chronic atropine administration on VIP levels in rat heart atria was investigated in relation to heart rate in the course of vagus nerves stimulation. Anaesthetised control and atropinised (10 mg/kg/day for 10 days) rats pretreated with metipranolol and phentolamine that were either given or not a single dose of atropine were subjected to bilateral vagus nerve stimulation (30 min: 0.7 mA, 20 Hz, 0.2 ms). VIP concentrations in the atria were determined after each stimulation protocol. In control rats with or without single atropine administration, the heart rate upon vagal stimulation was higher than in atropinised animals with or without single atropine dose, respectively. VIP concentrations in the control atria were significantly decreased after the stimulation; the decrease was comparable both in the absence and presence of a single dose of atropine. Compared to controls, VIP levels were significantly decreased after chronic atropine treatment and they were not further reduced by vagal stimulation and single atropine administration. Administration of VIP antagonist completely abolished the differences in the heart rate upon vagal stimulation between control and atropinised groups. In conclusion, the data indicate that chronic atropine administration affects VIP synthesis in rat heart atria and consequently it modifies the heart rate regulation.
- MeSH
- alfa blokátory farmakologie MeSH
- antagonisté hormonů farmakologie MeSH
- antagonisté muskarinových receptorů aplikace a dávkování MeSH
- atropin aplikace a dávkování MeSH
- beta blokátory farmakologie MeSH
- časové faktory MeSH
- elektrická stimulace MeSH
- fentolamin farmakologie MeSH
- krysa rodu Rattus MeSH
- metipranolol farmakologie MeSH
- nervus vagus účinky léků metabolismus MeSH
- potkani Wistar MeSH
- receptory muskarinové účinky léků metabolismus MeSH
- srdeční frekvence účinky léků MeSH
- srdeční síně inervace metabolismus MeSH
- vazoaktivní intestinální peptid antagonisté a inhibitory metabolismus farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- alfa blokátory MeSH
- antagonisté hormonů MeSH
- antagonisté muskarinových receptorů MeSH
- atropin MeSH
- beta blokátory MeSH
- fentolamin MeSH
- metipranolol MeSH
- receptory muskarinové MeSH
- vasoactive intestinal peptide, 4-chloro-Phe(6)-Leu(17)- MeSH Prohlížeč
- vazoaktivní intestinální peptid MeSH
Vasoactive intestinal peptide (VIP) is a vasorelaxant peptide that addresses two receptor subtypes, VPAC1 and VPAC2. It stimulates insulin secretion and mediates anti-inflammatory effects and has been proposed for treatment of type 2 and autoimmune diabetes. In the heart, VIP is produced and released primarily by intrinsic neurons and improves cardiac perfusion and function. Here, we investigated the involvement of this system in the events underlying development of experimentally induced diabetic cardiomyopathy. Rats received a single streptozotocin injection, and cardiac VIP content [radioimmune assay (RIA)], expression of the VIP precursors VPAC1 and VPAC2 [real-time reverse transcription-polymerase chain reaction (RT-PCR)], and VPAC1 and VPAC2 tissue distribution (immunohistochemistry) were assessed 4, 8, and 16 weeks thereafter and compared with corresponding vehicle-treated controls. Cardiac neuropathy manifests progressively during the first 4 months of diabetes at the preproVIP mRNA and VIP peptide level and is accompanied by initial down-regulation of VPAC2 at one prime target of VIP-containing axons, i.e., smooth muscle cells of coronary arterioles. VPAC1 is expressed by macrophages. After initial changes that are specific for atria and ventricles, respectively, VPAC1 and VPAC2 expression return to control levels at 16 weeks despite ongoing loss of VIP. Given the cardioprotective role of the VIP signaling system, the persistence of receptors has therapeutic implications since it is the prerequisite for trials with VPAC2 agonists.
- MeSH
- down regulace * MeSH
- experimentální diabetes mellitus komplikace metabolismus patologie MeSH
- imunohistochemie MeSH
- kardiomyocyty metabolismus patologie MeSH
- kardiomyopatie etiologie metabolismus patologie MeSH
- krysa rodu Rattus MeSH
- myokard metabolismus patologie MeSH
- peritoneální makrofágy metabolismus patologie MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- proteinové prekurzory biosyntéza metabolismus MeSH
- radioimunoanalýza MeSH
- receptory vazoaktivního intestinálního peptidu typu I biosyntéza MeSH
- receptory vazoaktivního intestinálního peptidu typu II biosyntéza MeSH
- srdeční komory metabolismus MeSH
- vazoaktivní intestinální peptid biosyntéza MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- proteinové prekurzory MeSH
- receptory vazoaktivního intestinálního peptidu typu I MeSH
- receptory vazoaktivního intestinálního peptidu typu II MeSH
- vazoaktivní intestinální peptid MeSH
Vasoactive intestinal peptide (VIP) is a neuropeptide released from the autonomic nerves exerting multiple antiinflammatory effects. The aim of the present study was to investigate the impact of severe sepsis and hemofiltration in two settings on plasma and tissue concentrations of VIP in a porcine model of sepsis. Thirty-two pigs were divided into 5 groups: 1) control group; 2) control group with conventional hemofiltration; 3) septic group; 4) septic group with conventional hemofiltration; 5) septic group with high-volume hemofiltration. Sepsis induced by faecal peritonitis continued for 22 hours. Hemofiltration was applied for the last 10 hours. Hemodynamic, inflammatory and oxidative stress parameters (heart rate, mean arterial pressure, cardiac output, systemic vascular resistance, plasma concentrations of tumor necrosis factor-alpha, interleukin-6, thiobarbituric acid reactive species, nitrate + nitrite, asymmetric dimethylarginine) and the systemic VIP concentrations were measured before faeces inoculation and at 12 and 22 hours of peritonitis. VIP tissue levels were determined in the left ventricle, mesenteric and coronary arteries. Sepsis induced significant increases in VIP concentrations in the plasma and mesenteric artery, but it decreased peptide levels in the coronary artery. Hemofiltration in both settings reduced concentrations of VIP in the mesenteric artery. In severe sepsis, VIP seems to be rapidly depleted from the coronary artery and, on the other hand, upregulated in the mesenteric artery. Hemofiltration in both settings has a tendency to drain away these upregulated tissue stores which could result in the limited secretory capacity of the peptide.
- MeSH
- arteriae mesentericae metabolismus MeSH
- hemofiltrace * MeSH
- koronární cévy metabolismus MeSH
- oxidační stres MeSH
- peritonitida komplikace MeSH
- prasata MeSH
- sepse etiologie metabolismus patofyziologie MeSH
- vazoaktivní intestinální peptid krev genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- vazoaktivní intestinální peptid MeSH
The effects of melatonin on basal and vasoactive intestinal peptide (VIP)-induced cAMP concentration was studied in dispersed cells of the rat suprachiasmatic nuclei (SCN). Our data indicate, that VIP induces a rapid increase of cAMP concentration in the cells followed by a slow and prolonged increase in the medium. The VIP-induced increase was dose-dependent in the range of 1-100 nM. Melatonin had no effect on basal cAMP but inhibited the cAMP increase induced by VIP in a dose-dependent manner (EC50 = 0.21 nM). Our observations indicate that melatonin acts through the inhibition of cAMP in the SCN cells similar as shown in other tissues.
- MeSH
- AMP cyklický metabolismus MeSH
- antioxidancia farmakologie MeSH
- cirkadiánní rytmus fyziologie MeSH
- krysa rodu Rattus MeSH
- melatonin farmakologie MeSH
- neurony účinky léků metabolismus MeSH
- nucleus suprachiasmaticus cytologie MeSH
- potkani Wistar MeSH
- vazoaktivní intestinální peptid farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- AMP cyklický MeSH
- antioxidancia MeSH
- melatonin MeSH
- vazoaktivní intestinální peptid MeSH
Chronic diarrhea is a significant challenge in clinical practice because of its high prevalence and various causes. Comprehensive clinical assessment and stepwise laboratory approach are crucial for an accurate diagnosis. This report presents a case of an adult woman who experienced chronic watery diarrhea, complicated by renal impairment and multiple electrolyte imbalances, including hypokalemia, hypophosphatemia, and metabolic acidosis. The diagnosis of a vasoactive intestinal polypeptide-secreting tumor (VIPoma) with liver metastases was confirmed by elevated serum levels of a vasoactive intestinal polypeptide (VIP) and imaging findings of a pancreatic mass with multiple hepatic lesions. Preoperative management, including fluid rehydration, electrolyte correction, and somatostatin analog therapy, significantly improved her clinical symptoms. Subsequent surgical tumor removal and radiofrequency ablation of the hepatic lesions resulted in complete resolution of symptoms and normalized VIP levels. This case emphasizes the importance of early recognition of this rare tumor in patients with chronic diarrhea to improve clinical outcomes.
- Klíčová slova
- VIPoma, WDHA syndrome, chronic watery diarrhea, functional neuroendocrine tumor, vasoactive intestinal polypeptide,
- MeSH
- chronická nemoc MeSH
- diareogenní nádor * komplikace diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory jater sekundární komplikace MeSH
- nádory slinivky břišní * komplikace MeSH
- průjem * etiologie MeSH
- vazoaktivní intestinální peptid krev MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- vazoaktivní intestinální peptid MeSH
- MeSH
- gastrointestinální hormony metabolismus MeSH
- lidé MeSH
- vazoaktivní intestinální peptid metabolismus MeSH
- ženské pohlavní orgány metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- gastrointestinální hormony MeSH
- vazoaktivní intestinální peptid MeSH