BACKGROUND: An altered sympathetic nervous system is implicated in many cardiac pathologies, ranging from sudden infant death syndrome to common diseases of adulthood such as hypertension, myocardial ischemia, cardiac arrhythmias, myocardial infarction, and heart failure. Although the mechanisms responsible for disruption of this well-organized system are the subject of intensive investigations, the exact processes controlling the cardiac sympathetic nervous system are still not fully understood. A conditional knockout of the Hif1a gene was reported to affect the development of sympathetic ganglia and sympathetic innervation of the heart. This study characterized how the combination of HIF-1α deficiency and streptozotocin (STZ)-induced diabetes affects the cardiac sympathetic nervous system and heart function of adult animals. METHODS: Molecular characteristics of Hif1a deficient sympathetic neurons were identified by RNA sequencing. Diabetes was induced in Hif1a knockout and control mice by low doses of STZ treatment. Heart function was assessed by echocardiography. Mechanisms involved in adverse structural remodeling of the myocardium, i.e. advanced glycation end products, fibrosis, cell death, and inflammation, was assessed by immunohistological analyses. RESULTS: We demonstrated that the deletion of Hif1a alters the transcriptome of sympathetic neurons, and that diabetic mice with the Hif1a-deficient sympathetic system have significant systolic dysfunction, worsened cardiac sympathetic innervation, and structural remodeling of the myocardium. CONCLUSIONS: We provide evidence that the combination of diabetes and the Hif1a deficient sympathetic nervous system results in compromised cardiac performance and accelerated adverse myocardial remodeling, associated with the progression of diabetic cardiomyopathy.
- MeSH
- diabetická kardiomyopatie * genetika MeSH
- experimentální diabetes mellitus * chemicky indukované genetika komplikace MeSH
- myokard metabolismus MeSH
- myši MeSH
- srdce inervace MeSH
- sympatický nervový systém metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Východiská: Experimentálne a klinické štúdie preukázali, že v procesoch karcinogenézy, proliferácie nádorových buniek a tvorby metastáz zohráva významnú úlohu aj nervový systém. Tieto štúdie, zamerané na neurobiologické aspekty nádorových chorôb, objasňujú mechanizmy a dráhy, prostredníctvom ktorých nervový systém ovplyvňuje makroprostredie i mikroprostredie nádorov. Modulačný vplyv nervového systému na mikroprostredie nádoru sprostredkúvajú vo významnej miere nervy, ktoré inervujú nádorové tkanivo. Inervácia nádorového tkaniva je už v súčasnosti akceptovaný fakt, pričom viacerí autori ju považujú za ďalšiu základnú charakteristiku nádorových chorôb. Cieľ: Zámerom tohto prehľadového článku je priblížiť súčasný pohľad na úlohu inervácie nádorového tkaniva, ako aj z toho vyplývajúce terapeutické konsekvencie. Záver: Na základe súčasných poznatkov je možné konštatovať, že inervácia nádorového tkaniva predstavuje jeden z významných faktorov etiopatogenézy nádorových chorôb a potenciálny cieľ nových terapeutických intervencií u onkologických pacientov.
Background: Experimental and clinical studies have shown that the nervous system also plays an important role in the processes of carcinogenesis, cancer cell proliferation, and metastasis. These studies, focused on the neurobiological aspects of cancer, elucidate the mechanisms and pathways by which the nervous system affects tumor macro- and microenvironment. The modulatory effect of the nervous system on the tumor microenvironment is significantly mediated by nerves that innervate cancer tissue. The innervation of cancer tissue is already an accepted fact, and several authors consider it to be another hallmark of cancer. Purpose: The aim of this review article is to present a recent data about the role of innervation of cancer tissue, as well as to describe therapeutic consequences. Conclusion: Based on recent data, it can be concluded that the innervation of cancer tissue represents an important factor in the etiopathogenesis of cancer as well as a potential target for new therapeutic interventions in cancer patients.
- MeSH
- lidé MeSH
- nádorové mikroprostředí MeSH
- nádory * metabolismus MeSH
- sympatický nervový systém * metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Obesity is associated with increased sympathetic nervous system activation, possibly contributing to higher cardiovascular risk. The aim of this study was to assess the relationship between body adiposity and sympathoadrenergic contractions in rat isolated mesenteric arteries, and the modulatory effect of mesenteric perivascular adipose tissue (PVAT). Experiments were performed on male 38-week-old Wistar, Zucker lean (ZL) and Zucker diabetic fatty (ZDF) rats. Paired rings of isolated rat superior mesenteric arteries with or without PVAT were prepared and connected to a force-displacement transducer for the recording of isometric tension. Contractile responses were elicited by increasing doses of exogenous noradrenaline and by endogenous noradrenaline released during electrical stimulation of perivascular adrenergic nerves. In ZDF rats, mesenteric PVAT had marked anticontractile effect leading to significant reduction in adrenergic contractions of their superior mesenteric arteries; however, in arterial preparations without PVAT, obese rats showed significantly increased sensitivity in their contractile responses to adrenergic stimulation when compared to other rat groups. In Wistar rats, ranging in the level of body adiposity between ZL and ZDF rats, neurogenic contractions in arterial preparations with preserved PVAT were higher compared to those without PVAT. No vasomodulatory effect of PVAT was detected in mesenteric arteries from ZL rats. The results of this study indicate that the modulatory effect of mesenteric PVAT on arterial adrenergic contractions did not change in proportion with increasing adiposity; however, it could be influenced by the rat strain-specific distribution of sympathetic nerves between PVAT and the proper mesenteric arterial wall. In ZDF rats, characterized by higher vascular sympathetic tone, the mesenteric arteries might be specifically regulated by the anticontractile effect of PVAT, leading to higher mesenteric blood flow. This could be associated with hyperphagia and increased nutrient-induced mesenteric vasodilatation in this rat strain.
- MeSH
- adipozita * MeSH
- arteria mesenterica superior inervace MeSH
- druhová specificita MeSH
- elektrická stimulace MeSH
- modely nemocí na zvířatech MeSH
- noradrenalin farmakologie MeSH
- obezita patofyziologie MeSH
- potkani Wistar MeSH
- potkani Zucker MeSH
- sympatický nervový systém účinky léků metabolismus patofyziologie MeSH
- vazokonstrikce * účinky léků MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
Existing experimental studies of the effect of sympathetic nerve fibers on bone marrow cells are based on the systemic administration of neurotoxic 6-hydroxydopamine. The method of global chemical sympathectomy has some serious disadvantages and could lead to questionable results. We describe a new method of local chemical sympathectomy of rat femoral bone marrow using guanethidine (Ismelin) delivery using an osmotic mini pump. Local guanethidine treatment for 14days led to complete elimination of sympathetic fibers in femoral bone marrow in contrast to bone marrow of contralateral or naïve femurs. Ablation of sympathetic fibers was associated with a loss of rat endothelial cell marker (RECA) indicating immunophenotype changes in blood vessel endothelial cells, but no significant effect of guanethidine was found on the survival of endothelial cells and mesenchymal stem cells in vitro. Moreover, local guanethidine treatment also elicited a significant reduction of Nestin+/SDF1+ mesenchymal stem cells and c-Kit+/CD90+ hematopoietic stem cells in femoral bone marrow. Tissue-specific chemical sympathectomy of rat bone marrow by guanethidine overcomes some of the drawbacks of systemic administration of neurotoxic compounds like 6-hydroxydopamine and delivers unequivocal evidence on the effects of sympathetic innervation on the cell content of bone marrow.
- MeSH
- endoteliální buňky pupečníkové žíly (lidské) účinky léků metabolismus patologie MeSH
- femur účinky léků inervace metabolismus patologie MeSH
- fluorescenční protilátková technika MeSH
- guanethidin farmakologie MeSH
- kostní dřeň účinky léků inervace metabolismus MeSH
- lidé MeSH
- mezenchymální kmenové buňky účinky léků metabolismus patologie MeSH
- modely u zvířat MeSH
- potkani Wistar MeSH
- průtoková cytometrie MeSH
- sympatektomie chemická MeSH
- sympatický nervový systém účinky léků metabolismus patologie MeSH
- sympatolytika farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Calcium sensitization mediated by RhoA/Rho kinase pathway can be evaluated either in the absence (basal calcium sensitization) or in the presence of endogenous vasoconstrictor systems (activated calcium sensitization). Our aim was to compare basal and activated calcium sensitization in three forms of experimental hypertension with increased sympathetic tone and enhanced calcium entry-spontaneously hypertensive rats (SHR), heterozygous Ren-2 transgenic rats (TGR), and salt hypertensive Dahl rats. Activated calcium sensitization was determined as blood pressure reduction induced by acute administration of Rho kinase inhibitor fasudil in conscious rats with intact sympathetic nervous system (SNS) and renin-angiotensin system (RAS). Basal calcium sensitization was studied as fasudil-dependent difference in blood pressure response to calcium channel opener BAY K8644 in rats subjected to RAS and SNS blockade. Calcium sensitization was also estimated from reduced development of isolated artery contraction by Rho kinase inhibitor Y-27632. Activated calcium sensitization was enhanced in all three hypertensive models (due to the hyperactivity of vasoconstrictor systems). In contrast, basal calcium sensitization was reduced in SHR and TGR relative to their controls, whereas it was augmented in salt-sensitive Dahl rats relative to their salt-resistant controls. Similar differences in calcium sensitization were seen in femoral arteries of SHR and Dahl rats.
- MeSH
- geneticky modifikovaná zvířata MeSH
- hypertenze etiologie genetika metabolismus patologie MeSH
- kinázy asociované s rho antagonisté a inhibitory genetika MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- potkani inbrední Dahl MeSH
- potkani inbrední SHR MeSH
- signální transdukce účinky léků MeSH
- sympatický nervový systém metabolismus patologie MeSH
- vápník aplikace a dávkování metabolismus MeSH
- vazokonstrikce genetika MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Cílem moderní léčby diabetu je přiblížit se co nejvíce normálním hodnotám glykemie. Limitem současné farmakologické léčby však jsou hypoglykemické epizody, jež mohou narušovat každodenní život a v extrémním případě vést i ke smrti. Rizikovým faktorem pro vznik hypoglykemie je tzv. syndrom porušeného vnímání hypoglykemie, který komplikuje 5–10 % případů dlouhotrvajícího diabetu 1. typu a vyskytuje se i u diabetu 2. typu závislého na léčbě inzulinem. Nadměrná dávka inzulinu není vyrovnána včasnou kontraregulační sekrecí glukagonu v A buňkách pankreatu a zároveň je porušena centrální aktivace sympatoadrenálního systému. V důsledku toho nejenže nedochází k dostatečné novotvorbě glukózy v játrech, ale chybějí také varovné stresové příznaky, které pacienta upozorňují na nutnost perorálního příjmu cukru. Opakované hypoglykemie vedou k tomu, že se dále snižuje nastavení centrálních receptorů glykemie a porucha se prohlubuje. Ke zlepšení tohoto stavu může vést důsledné předcházení rekurentním poklesům hladiny glukózy, jež se ovšem musí opírat o intenzivní monitorování glykemie. Reálnou možnost pro léčbu syndromu porušeného vnímání hypoglykemie představuje obnova endogenní sekrece inzulinu transplantací celého pankreatu nebo izolovaných Langerhansových ostrůvků.
The aim of modern treatment of diabetes is to achieve blood glucose levels that are as close to physiological levels as possible. However, limitations of current pharmacological treatments are represented by hypoglycaemic episodes, which can interfere with daily life and in extreme cases even lead to death. The so-called hypoglycaemia unawareness syndrome represents a risk factor for hypoglycaemia, complicating as it does 5-10 % cases of long-standing type 1 diabetes and occurring even in insulin-dependent type 2 diabetes. Occasional excessive levels of subcutaneously administered insulin are not balanced by the immediate release of glucagon in A cells of the pancreas and by central activation of the sympathetic-adrenal system. Consequently, the release of endogenous glucose from the liver is impaired and the missing typical signs of hypoglycaemia do not warn the patient that oral intake of sugar is needed. Repeated hypoglycaemia further lowers the setting of central glucose receptors and the disorder is further aggravated. Improvement lies in the meticulous prevention of hypoglycaemia based on intensive blood glucose monitoring and patient education. A realistic treatment option of advanced hypoglycaemia unawareness syndrome involves the restoration of endogenous insulin secretion by pancreas or pancreatic islet transplantation.
- MeSH
- adrenalin metabolismus sekrece MeSH
- deformace percepce fyziologie MeSH
- diabetes mellitus 1. typu * farmakoterapie komplikace MeSH
- diabetes mellitus 2. typu farmakoterapie komplikace MeSH
- glukagon metabolismus sekrece MeSH
- hypoglykemie * chemicky indukované metabolismus prevence a kontrola MeSH
- inzulin metabolismus škodlivé účinky MeSH
- krevní glukóza metabolismus účinky léků MeSH
- lidé MeSH
- sympatický nervový systém fyziologie metabolismus MeSH
- syndrom MeSH
- uvědomování si * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
The ability to predict the success or failure of smoking cessation efforts will be useful for clinical practice. Stress response is regulated by two primary neuroendocrine systems. Salivary cortisol has been used as a marker for the hypothalamuspituitary- adrenocortical axis and salivary ?-amylase as a marker for the sympathetic adrenomedullary system. We studied 62 chronic smokers (34 women and 28 men with an average age of 45.2±12.9 years). The levels of salivary cortisol and salivary ?-amylase were measured during the period of active smoking, and 6 weeks and 24 weeks after quitting. We analyzed the men separately from the women. The men who were unsuccessful in cessation showed significantly higher levels of salivary ?-amylase over the entire course of the cessation attempt. Before stopping smoking, salivary cortisol levels were higher among the men who were unsuccessful in smoking cessation. After quitting, there were no differences between this group and the men who were successful in cessation. In women we found no differences between groups of successful and unsuccessful ex-smokers during cessation. In conclusions, increased levels of salivary ?- amylase before and during smoking cessation may predict failure to quit in men. On the other hand, no advantage was found in predicting the failure to quit in women. The results of our study support previously described gender differences in smoking cessation.
- MeSH
- alfa-amylasy metabolismus MeSH
- biologické markery metabolismus MeSH
- dospělí MeSH
- financování organizované MeSH
- hydrokortison metabolismus MeSH
- kouření metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- neúspěšná terapie MeSH
- odvykání kouření MeSH
- pohlavní dimorfismus MeSH
- prediktivní hodnota testů MeSH
- sliny enzymologie MeSH
- sympatický nervový systém metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- srovnávací studie MeSH
- Klíčová slova
- signální systémy CNS, periferní regulace, energetická rovnováha,
- MeSH
- adipozita fyziologie MeSH
- centrální nervový systém fyziologie MeSH
- energetický metabolismus * fyziologie MeSH
- energetický příjem * fyziologie MeSH
- nadledviny fyziologie metabolismus MeSH
- nervový přenos fyziologie MeSH
- nucleus arcuatus hypothalami fyziologie MeSH
- nucleus solitarius fyziologie MeSH
- psychický stres MeSH
- regulace chuti k jídlu * fyziologie MeSH
- signální transdukce fyziologie MeSH
- sympatický nervový systém fyziologie metabolismus MeSH
- sympatoadrenální systém MeSH
- tělesná hmotnost * fyziologie MeSH
- tuková tkáň fyziologie metabolismus MeSH
Compression of the rostral ventrolateral medulla oblongata (RVLM) by an abnormally located artery is regarded as one possible cause of arterial hypertension. There exists a limited set of data suggesting that increased sympathetic activity in patients with RVLM compression may lead to arterial hypertension. Accordingly, we decided to assess the sympathetic activity in patients with severe arterial hypertension and to investigate any correlation with the presence of RVLM compression. Sixty-four patients with severe arterial hypertension were enrolled in our study. Sympathetic activity was evaluated using 24-hour urinary norepinephrine as measured by high-pressure liquid chromatography with electrochemical detection. The presence of RVLM compression was assessed with magnetic resonance imaging. Neurovascular compression of the RVLM was identified in 40 patients, 27 of whom presented left-sided compression. Twenty-four hour urinary norepinephrine averaged 263.6±135.9 nmol in patients with neurovascular compression - 255.6±137.3 nmol in those with left-sided compression and 251.6±138.5 nmol in patients without RVLM compression. We did not identify any increase in urinary norepinephrine in patients with severe arterial hypertension and neurovascular compression of the RVLM. Our results do not support the hypothesis that neurovascular compression of RVLM may exhibit a sympathetically mediated increase in blood pressure.
- MeSH
- časové faktory MeSH
- dospělí MeSH
- elektrochemické techniky MeSH
- financování organizované MeSH
- hypertenze moč patofyziologie patologie MeSH
- krevní tlak MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- medulla oblongata patofyziologie patologie MeSH
- noradrenalin moč MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- sympatický nervový systém metabolismus patofyziologie MeSH
- úžinové syndromy moč patofyziologie patologie MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
Poruchy príjmu potravy patria medzi závažné medicínske ochorenia v detskom a adolescentnom veku. Do popredia vystupuje zmena hmotnosti – obezita alebo podvýživa (napr. pri mentálnej anorexii), ktoré majú vplyv na takmer všetky fyziologické funkcie organizmu vrátane aktivity autonómneho nervového systému. V súčasnosti je málo prác, zaoberajúcich sa problematikou mentálnej anorexie a zmien autonómneho nervového systému. Typickým nálezom pri mentálnej anorexii je bradykardia so zvýšenou parasympatikovou aktivitou, ktorá sa však pri dlhšom trvaní ochorenia môže výrazne až abnormálne znížiť. Závery týkajúce sa hodnotenia sympatikovej aktivity nie sú zatiaľ jednoznačné. Na sledovanie zmien aktivity sympatikovej a parasympatikovej časti autonómneho nervového systému sa v súčasnosti používajú lineárne a nelineárne metódy analýzy variability frekvencie srdca a tlaku krvi, ako aj vyšetrenie kardiovaskulárnych testov. Aj kvôli pokračujúcemu nárastu a závažnosti porúch príjmu potravy v detskom a adolescentnom veku je potrebné pokračovať v monitorovaní zmien aktivity autonómneho nervového systému, ako aj sledovať efekt liečby a terapeutických postupov.
Disorders of food intake belong to serious medical diseases at the child and adolescent age. The most prominent symptom is changed body mass – obesity or malnutrition (e.g. in mental anorexia), which influence almost all physiological functions of the organism including activity of autonomic nervous system. At the present time there are few papers dealing with the problem of mental anorexia and changes in autonomic nervous system. Bradycardia with increased parasympathetic activity is a typical finding in mental anorexia and may decrease significantly or even abnormally after some time. The conclusions concerning the evaluation of sympathetic activity are not unambiguous. The determination of changes in the activity of sympathetic and parasympathetic part of autonomic nervous system presently employs linear and nonlinear methods for analysis of variability in heart rate and blood pressure as well as the examination by cardiovascular tests. It is also for the increasing rate and severity of food intake disorders at the child and adolescent age that monitoring of the changes in autonomic nervous activity should be continued and the effects of therapy and therapeutic procedures should be investigated.
- MeSH
- autonomní nervový systém patofyziologie patologie MeSH
- bradykardie diagnóza etiologie MeSH
- finanční podpora výzkumu jako téma MeSH
- komorbidita MeSH
- krevní tlak genetika MeSH
- lidé MeSH
- mentální anorexie komplikace metabolismus MeSH
- nemoci autonomního nervového systému etiologie MeSH
- parasympatický nervový systém abnormality fyziologie metabolismus MeSH
- srdeční frekvence fyziologie MeSH
- sympatický nervový systém abnormality fyziologie metabolismus MeSH
- Check Tag
- lidé MeSH