AIMS: To investigate the therapeutic potential of visual stimulation (VS) and BDNF in murine experimental autoimmune uveoretinitis (EAU). MAIN METHODS: Mice were immunized by subcutaneous injection of interphotoreceptor retinoid-binding protein in Freund's complete adjuvant and intravenous injection of pertussis toxin, and were then exposed to high-contrast VS 12 h/day (days 1-14 post-immunization). EAU severity was assessed by examining clinical score, visual acuity, inflammatory markers, and immune cells in the retina. The transcriptome of activated retinal cells was determined by RNA-seq using RNA immunoprecipitated in complex with phosphorylated ribosomal protein S6. The retinal levels of protein products of relevant upregulated genes were quantified. The effect of BDNF on EAU was tested in unstimulated mice by its daily topical ocular administration (days 8-14 post-immunization). KEY FINDINGS: VS attenuated EAU development and decreased the expression of pro-inflammatory cytokines/chemokines and numbers of immune cells in the retina (n = 10-20 eyes/group for each analysis). In activated retinal cells of control mice (n = 30 eyes/group), VS upregulated genes encoding immunomodulatory neuropeptides, of which BDNF and vasoactive intestinal peptide (VIP) also showed increased mRNA and protein levels in the retina of VS-treated EAU mice (n = 6-10 eyes/group for each analysis). In unstimulated EAU mice, BDNF treatment mimicked the protective effects of VS by modulating the inflammatory and stem cell properties of Müller cells (n = 5 eyes/group for each analysis). SIGNIFICANCE: VS effectively suppresses EAU, at least through enhancing retinal levels of anti-inflammatory and neuroprotective factors, VIP and BDNF. Our findings also suggest BDNF as a promising therapeutic agent for uveitis treatment.
- MeSH
- autoimunitní nemoci * imunologie metabolismus MeSH
- cytokiny metabolismus MeSH
- modely nemocí na zvířatech MeSH
- mozkový neurotrofický faktor * metabolismus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- retina metabolismus účinky léků MeSH
- retinitida * farmakoterapie prevence a kontrola imunologie MeSH
- uveitida * metabolismus farmakoterapie imunologie MeSH
- vazoaktivní intestinální peptid farmakologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The use of oxygen therapy (high doses of oxygen - hyperoxia) in the treatment of premature infants results in their survival. However, it also results in a high incidence of chronic lung disease known as bronchopulmonary dysplasia, a disease in which airway hyper-responsiveness and pulmonary hypertension are well known as consequences. In our previous studies, we have shown that hyperoxia causes airway hyper-reactivity, characterized by an increased constrictive and impaired airway smooth muscle relaxation due to a reduced release of relaxant molecules such as nitric oxide, measured under in vivo and in vitro conditions (extra- and intrapulmonary) airways. In addition, the relaxation pathway of the vasoactive intestinal peptide (VIP) and/or pituitary adenylate cyclase activating peptide (PACAP) is another part of this system that plays an important role in the airway caliber. Peptide, which activates VIP cyclase and pituitary adenylate cyclase, has prolonged airway smooth muscle activity. It has long been known that VIP inhibits airway smooth muscle cell proliferation in a mouse model of asthma, but there is no data about its role in the regulation of airway and tracheal smooth muscle contractility during hyperoxic exposure of preterm newborns.
- MeSH
- bronchopulmonální dysplazie etiologie metabolismus patofyziologie MeSH
- gestační stáří MeSH
- hladké svalstvo metabolismus patofyziologie MeSH
- hyperoxie etiologie metabolismus patofyziologie MeSH
- hypofyzární adenylátcyklázu aktivující peptid metabolismus MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- novorozená zvířata MeSH
- novorozenec nedonošený * MeSH
- novorozenec MeSH
- oxygenoterapie škodlivé účinky MeSH
- plíce metabolismus patofyziologie MeSH
- předčasný porod * MeSH
- remodelace dýchacích cest MeSH
- signální transdukce MeSH
- vazoaktivní intestinální peptid metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- MeSH
- adenosintrifosfát * farmakologie MeSH
- hypofyzární adenylátcyklázu aktivující peptid * farmakologie MeSH
- laboratorní zvířata MeSH
- lidé MeSH
- neuropeptid Y * farmakologie MeSH
- oxid dusnatý * farmakologie MeSH
- parasympatický nervový systém * MeSH
- převodní systém srdeční * MeSH
- serotonin * farmakologie MeSH
- srdce * inervace MeSH
- substance P * farmakologie MeSH
- sympatický nervový systém * MeSH
- tachykininy * farmakologie MeSH
- vazoaktivní intestinální peptid * farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem 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 genetika krev metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem 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.
- Klíčová slova
- Vasoactive intestinal polypeptide, Atropine, Heart atria, Vagus nerve stimulation, Rat,
- 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
- financování organizované MeSH
- krysa rodu rattus MeSH
- metipranolol farmakologie MeSH
- nervus vagus metabolismus účinky léků MeSH
- potkani Wistar MeSH
- receptory muskarinové metabolismus účinky léků MeSH
- srdeční frekvence účinky léků MeSH
- srdeční síně inervace metabolismus MeSH
- vazoaktivní intestinální peptid antagonisté a inhibitory farmakologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
Vasoactive intestinal peptide (VIP) is a 28-amino acid peptide that belongs to a family of structurally related peptide hormones including pituitary adenylate cyclase-activating peptide (PACAP). These hormones are widely distributed in the nervous system, where they act as neurotransmitters. Their biological effects are mediated by specific receptors, VPAC1 and VPAC2, which have comparable affinity for VIP and PACAP, and PAC1, which binds VIP with 1,000-fold lower affinity than PACAP. Both peptides are involved in autonomic regulation of the cardiovascular system, where they exert positive inotropic and chronotropic effects, and cause coronary vasodilatation. Additionally, PACAP inhibits proliferation of cardiac fibroblasts. Several cardiovascular diseases, such as myocardial fibrosis, heart failure, cardiomyopathy and pulmonary hypertension, have been found to be associated with changes in myocardial VIP concentration or with alteration of affinity, density and physiological responsiveness of VIP/PACAP receptors. Application of the peptides or their agonists has beneficial effect in hypertension, heart failure and myocardial fibrosis. Taken together, VIP and PACAP have beneficial effects in various pathological conditions.
- MeSH
- hypofyzární adenylátcyklázu aktivující peptid metabolismus MeSH
- hypofyzární polypeptid aktivující adenylátcyklasu - receptory typu I metabolismus MeSH
- hypofyzární polypeptid aktivující adenylátcyklasu - receptory MeSH
- receptory vazoaktivního intestinálního peptidu typu I * metabolismus MeSH
- receptory vazoaktivního intestinálního peptidu typu II metabolismus MeSH
- vazoaktivní intestinální peptid * metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
Vasoactive intestinal peptide (VIP) is a 28-amino acid peptide that belongs to a family of structurally related peptide hormones including pituitary adenylate cyclase-activating peptide (PACAP). These hormones are widely distributed in the nervous system, where they act as neurotransmitters. Their biological effects are mediated by specific receptors, VPAC1 and VPAC2, which have comparable affinity for VIP and PACAP, and PAC1, which binds VIP with 1,000-fold lower affinity than PACAP. Both peptides are involved in autonomic regulation of the cardiovascular system, where they exert positive inotropic and chronotropic effects, and cause coronary vasodilatation. Additionally, PACAP inhibits proliferation of cardiac fibroblasts. Several cardiovascular diseases, such as myocardial fibrosis, heart failure, cardiomyopathy and pulmonary hypertension, have been found to be associated with changes in myocardial VIP concentration or with alteration of affinity, density and physiological responsiveness of VIP/PACAP receptors. Application of the peptides or their agonists has beneficial effect in hypertension, heart failure and myocardial fibrosis. Taken together, VIP and PACAP have beneficial effects in various pathological conditions. (c) 2005 Prous Science. All rights reserved.
- MeSH
- autonomní nervový systém metabolismus MeSH
- cévy inervace metabolismus MeSH
- ganglia parasympatická metabolismus MeSH
- hypofyzární adenylátcyklázu aktivující peptid metabolismus MeSH
- hypofyzární polypeptid aktivující adenylátcyklasu - receptory typu I metabolismus MeSH
- kardiotonika terapeutické užití MeSH
- kardiovaskulární nemoci etiologie metabolismus prevence a kontrola MeSH
- kardiovaskulární systém inervace metabolismus MeSH
- lidé MeSH
- myokard metabolismus MeSH
- plicní hypertenze etiologie metabolismus prevence a kontrola MeSH
- receptory vazoaktivního intestinálního peptidu typu I metabolismus MeSH
- receptory vazoaktivního intestinálního peptidu typu II metabolismus MeSH
- signální transdukce MeSH
- srdeční selhání etiologie metabolismus prevence a kontrola MeSH
- vazoaktivní intestinální peptid metabolismus terapeutické užití MeSH
- vazodilatace účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- MeSH
- bolest farmakoterapie genetika MeSH
- cvičení MeSH
- elektroakupunktura MeSH
- indomethacin MeSH
- intravenózní anestezie MeSH
- kapsaicin MeSH
- ketamin MeSH
- lidé MeSH
- sexuální faktory MeSH
- vazoaktivní intestinální peptid MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- kongresy MeSH
- MeSH
- experimentální diabetes mellitus patofyziologie MeSH
- finanční podpora výzkumu jako téma MeSH
- krysa rodu rattus MeSH
- neuropeptid Y analýza MeSH
- peptid spojený s genem pro kalcitonin analýza MeSH
- poranění srdce MeSH
- srdce MeSH
- vazoaktivní intestinální peptid analýza MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- kongresy MeSH
