Sympathetic hyperactivity and relative NO deficiency are characteristic alterations in both genetic and salt hypertension. The contribution of these abnormalities to blood pressure (BP) maintenance can be determined in conscious rats using a consecutive blockade of particular vasoactive systems. Thus, the contribution of pressor effects of angiotensin II to the maintenance of high BP is usually small, but the role of renin-angiotensin system in the development of hypertension mediated by central and peripheral effects of angiotensin II on sympathetic activity is highly important. This is even true in angiotensin-dependent hypertension of heterozygous Ren-2 transgenic rats in which sympathetic hyperactivity is increasing with age. Central sympathoexcitation in this hypertensive model can be inhibited by lower losartan doses than peripheral angiotensin II-dependent vasoconstriction. This experimental model also yielded important knowledge on nephroprotective effects of new therapeutic drugs - endothelin receptor type A blockers. A considerable part of sympathetic vasoconstriction is dependent on the interaction of Ca2+ sensitization (RhoA/Rho kinase pathway) and Ca2+ influx (through L-VDCC). The blockade of these pathways prevents a major part of sympathetic vasoconstriction. Ca2+ sensitization seems to be attenuated in genetic hypertension in order to compensate increased Ca2+ influx. In contrast, enhanced Ca2+ sensitization is a hallmark of salt sensitivity in Dahl rats in which salt hypertension is dependent on increased Ca2+ influx. The attention should also be paid to the impairment of arterial baroreflex sensitivity which permits enhanced BP responses to pressor or depressor stimuli. Some abnormalities can be studied in blood vessels isolated from hypertensive rats but neither conduit arteries nor mesenteric resistance arteries represent the vascular beds decisive for the increased peripheral resistance and high BP. Keywords: Sympathetic vasoconstriction, NO-dependent vasodilatation, Calcium sensitization, Calcium influx, Arterial baroreflex, Spontaneously hypertensive rats, Salt hypertensive Dahl rats, Ren-2 transgenic rats, RAS blockade, SNS blockade, NOS inhibition, Endothelin, Vascular contraction and relaxation, Isolated conduit and resistance arteries, EDCF, PGI2, BKCa channels.
- MeSH
- hypertenze * patofyziologie metabolismus MeSH
- krevní tlak účinky léků fyziologie MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- renin-angiotensin systém účinky léků fyziologie MeSH
- sympatický nervový systém patofyziologie účinky léků MeSH
- vazodilatace účinky léků fyziologie MeSH
- vazokonstrikce * účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Takotsubo syndrom je definován jako syndrom akutního srdečního selhání, který se klinicky velmi často projevuje jako akutní koronární syndrom. Charakteristickým klinickým znakem je přechodná dysfunkce levé komory srdeční. Spouštějícími faktory jsou relativně často akutní neurologická onemocnění, a tak se předpokládá, že v patofyziologii hraje významnou roli právě centrální nervová soustava. Tento přehledový článek si klade za cíl představit základní informace o takotsubo syndromu se zaměřením na velmi pravděpodobné patofyziologické mechanismy v ose mozek-srdce.
Takotsubo syndrome is defined as a syndrome of acute heart failure that is very often manifested clinically as acute coronary syndrome. Transient left ventricular dysfunction is a characteristic clinical feature. Acute neurological diseases are relatively frequently the triggering factors; thus, it is assumed that it is the central nervous system that plays a significant role in the pathophysiology. The review article aims to provide basic information on Takotsubo syndrome with a focus on the very likely pathophysiological mechanisms in the brain-heart axis.
- Klíčová slova
- moxonidin,
- MeSH
- antihypertenziva * farmakologie terapeutické užití MeSH
- hypertenze farmakoterapie MeSH
- klinická studie jako téma MeSH
- lidé MeSH
- obezita komplikace MeSH
- sympatický nervový systém patofyziologie MeSH
- výchova a vzdělávání MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- novinové články MeSH
- zprávy MeSH
- Klíčová slova
- moxonidin,
- MeSH
- antihypertenziva * farmakologie terapeutické užití MeSH
- hypertenze farmakoterapie MeSH
- klinická studie jako téma MeSH
- lidé MeSH
- obezita komplikace MeSH
- sympatický nervový systém patofyziologie MeSH
- výchova a vzdělávání MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- novinové články MeSH
- zprávy MeSH
Mitral valve prolapse (MVP) belongs to cardiac disorders characterized by impaired closure of mitral leaflets. We studied adolescent group of patients with MVP suffering from symptomatology that cannot be explained by mitral regurgitation alone. Several studies suggested that symptoms can be explained by autonomic, in particular sympathetic-linked dysfunction. Thus, we assessed non-invasive sympathetic indices of blood pressure and heart rate variability and electrodermal activity (EDA). Fifty-three adolescents with MVP (age: 15.1+/-0.4 years) and 43 healthy age- and gender-matched adolescents (age: 14.9+/-0.4 years) were examined. Blood pressure, heart rate and EDA were continuously recorded during 6-min rest. Evaluated parameters were: low frequency band of systolic blood pressure variability, systolic, diastolic and mean blood pressure, mean RR interval, cardiac sympathetic indices: symbolic dynamics (0V%), left ventricular ejection time (LVET), pre-ejection period (PEP), and EDA. Our findings revealed significantly higher systolic, diastolic, and mean blood pressure values, shortened mean RR interval, increased 0V%, and shortened LVET in MVP patients vs. controls (p=0.028, p<0.001, p=0.002, p<0.001, p=0.050, p<0.001; respectively). Our study revealed enhanced cardiovascular sympathetic regulation in adolescent MVP patients. We suggest that evaluation of non-invasive sympathetic parameters could represent potential biomarkers for early diagnosis of cardiovascular complications associated with MVP already at adolescent age.
- MeSH
- funkce levé komory srdeční MeSH
- galvanická kožní odpověď MeSH
- krevní tlak MeSH
- lidé MeSH
- mitrální insuficience diagnóza patofyziologie MeSH
- mladiství MeSH
- prognóza MeSH
- prolaps mitrální chlopně diagnóza patofyziologie MeSH
- srdce diagnostické zobrazování inervace MeSH
- srdeční frekvence MeSH
- studie případů a kontrol MeSH
- sympatický nervový systém patofyziologie MeSH
- věkové faktory MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
It is widely accepted that sympathetic nervous system plays a crucial role in the development of hypertension. On the other hand, the role of adrenal medulla (the adrenomedullary component of the sympathoadrenal system) in the development and maintenance of high blood pressure in man as well as in experimental models of hypertension is still controversial. Spontaneously hypertensive rats (SHR) are the most widely used animal model of human essential hypertension characterized by sympathetic hyperactivity. However, the persistence of moderately elevated blood pressure in SHR subjected to sympathectomy neonatally as well as the resistance of adult SHR to the treatment by sympatholytic drugs suggests that other factors (including enhanced activity of the adrenomedullary hormonal system) are involved in the pathogenesis of hypertension of SHR. This review describes abnormalities in adrenomedullary hormonal system of SHR rats starting with the hyperactivity of brain centers regulating sympathetic outflow, through the exaggerated activation of sympathoadrenal preganglionic neurons, to the local changes in chromaffin cells of adrenal medulla. All the above alterations might contribute to the enhanced release of epinephrine and/or norepinephrine from adrenal medulla. Special attention is paid to the alterations in the expression of genes involved in catecholamine biosynthesis, storage, release, reuptake, degradation and adrenergic receptors in chromaffin cells of SHR. The contribution of the adrenomedullary hormonal system to the development and maintenance of hypertension as well as its importance during stressful conditions is also discussed.
- MeSH
- dřeň nadledvin metabolismus patofyziologie MeSH
- hormony metabolismus MeSH
- hypertenze genetika metabolismus patofyziologie MeSH
- krevní tlak genetika MeSH
- lidé MeSH
- potkani inbrední SHR MeSH
- sympatický nervový systém patofyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
High dependency of arterial blood pressure (ABP) on enhanced sympathetic activity, which maintains vascular tone, leads to hypotension after hemodynamic insults that blunt the sympathetic activity. Therefore, we hypothesized that sympathovagal balance before tourniquet deflation (TD) determines the extent of a reduction in ABP after TD during total knee arthroplasty (TKA). Fifty-four hypertensive female patients undergoing TKA under spinal anesthesia were analyzed. The sympathovagal balance [low-to-high frequency ratio of heart rate variability (LF/HF)] before TD was defined as (LF/HF during 5 min before TD-preanesthetic LF/HF)/preanesthetic LF/HF (%). An increase in its value represents a shift in sympathovagal balance toward sympathetic predominance. The percent change in the mean ABP (MAP) after TD was defined as (minimum MAP during 10 min after TD-averaged MAP during 5 min before TD)/averaged MAP during 5 min before TD (%). Simple linear regression was performed to assess the correlation between the sympathovagal balance before TD and change in MAP after TD. The correlation was also assessed by multiple linear regression controlling for age, duration of tourniquet inflation, and spinal anesthesia-induced hypotension. Thirty-two minutes (on average) after tourniquet inflation, the MAP was decreased by 12.1 (-3.0 to 47.9) % [mean (range)] upon TD (P<0.001). The sympathovagal balance before TD was negatively proportional to the change in MAP after TD in both simple and multiple linear regression models (R2=0.323 and 0.340, P<0.001). A shift in sympathovagal balance toward sympathetic predominance before TD is associated with a decrease in ABP after TD.
- MeSH
- arteriální tlak * MeSH
- hypertenze patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nervus vagus patofyziologie MeSH
- peroperační doba MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- spinální anestezie MeSH
- srdeční frekvence MeSH
- stárnutí MeSH
- sympatický nervový systém patofyziologie MeSH
- totální endoprotéza kolene * MeSH
- turnikety * MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The sympathetic nerve activity (SNA) is augmented in hypertension. SNA is regulated by neuronal nitric oxide synthase (nNOS) or endothelial nitric oxide synthase (eNOS) activity in hypothalamic paraventricular nuclei (PVN) and/or brainstem rostral ventrolateral medulla. High nNOS or eNOS activity within these brain regions lowers the SNA, whereas low cerebral nNOS and/or eNOS activity causes SNA augmentation. We hypothesize that the decreased cerebral nNOS/eNOS activity, which allows the enhancement of SNA, leads to the augmentation of renal eNOS/nNOS activity. Similarly, when the cerebral nNOS/eNOS activity is increased and SNA is suppressed, the renal eNOS/nNOS activity is suppressed as well. The activation of endothelial alpha(2)-adrenoceptors, may be a possible mechanism involved in the proposed regulation. Another possible mechanism might be based on nitric oxide, which acts as a neurotransmitter that tonically activates afferent renal nerves, leading to a decreased nNOS activity in PVN. Furthermore, the importance of the renal nNOS/eNOSactivity during renal denervation is discussed. In conclusion, the presented hypothesis describes the dual organ-specific role of eNOS/nNOS activity in blood pressure regulation and suggests possible connection between cerebral NOS and renal NOS via activation or inhibition of SNA, which is an innovative idea in the concept of pathophysiology of hypertension.
- MeSH
- hypertenze enzymologie patofyziologie MeSH
- krevní tlak * MeSH
- ledviny enzymologie inervace MeSH
- lidé MeSH
- mozek enzymologie MeSH
- oxid dusnatý metabolismus MeSH
- sympatický nervový systém patofyziologie MeSH
- synthasa oxidu dusnatého, typ I metabolismus MeSH
- synthasa oxidu dusnatého, typ III metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- 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
Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
Nestr.
Brain and kidney play essential role in the pathogenesis of hypertension. Sympathetic nervous system (SNS) is a principle effector in the brain regulation of vascular tone and is also responsible for abnormal renal function in salt-sensitive hypertension (ß2-WNK4-NCC pathway). In contrast, renin-angiotensin system (RAS) is a major regulator of renal function in salt-resistant hypertension. It also modulates sympathetic vasoconstriction by its central and peripheral action. The aim of this project is to evaluate the role of these systems (especially ß2-WNK4-NCC pathway) in the development of several forms of experimental hypertension resembling human salt-sensitive or salt-resistant hypertension. The differences in SNS and RAS control of blood pressure, renal function and sodium homeostasis revealed in particular models might be used in a more detailed classification of human hypertension in order to discern the eligibility of hypertensive patients for particular therapeutic interventions – from standard pharmacological intervention to RAS and SNS to renal sympathetic denervation.
Mozek a ledviny hrají klíčovou úlohu v patogenezi hypertenze. Sympatický nervový systém (SNS) je hlavním efektorem mozkové regulace cévního tonu a je také odpovědný za abnormální funkci ledvin u sůl-sensitivní hypertenze (ß2-WNK4-NCC dráha). Naopak, renin-angiotensinový systém (RAS) je hlavním regulátorem funkce ledvin u sůl-resistentní hypertenze. RAS také moduluje sympatickou vasokonstrikci svými centrálními i periferními účinky. Cílem tohoto projektu je zhodnotit úlohu těchto systémů (se zvláštním zřetelem k ß2-WNK4-NCC dráze) při vývoji různých forem experimentální hypertenze podobajících se lidské sůl-sensitivní a sůl-resistentní hypertenzi. Rozdíly v úloze SNS a RAS při kontrole krevního tlaku, funkce ledvin a sodíkové homeostázy, které budou nalezeny u těchto modelů hypertenze, mohou být použity při detailnější klasifikaci lidské hypertenze s cílem určit vhodnost hypertenzních pacientů pro jednotlivé terapeutické přístupy (od standardních farmakologických zásahů do RAS a SNS až po renální sympatickou denervaci).
- MeSH
- hypertenze patofyziologie MeSH
- krevní tlak fyziologie MeSH
- ledviny patofyziologie MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- renin-angiotensin systém fyziologie MeSH
- sympatický nervový systém patofyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- kardiologie
- neurologie
- angiologie
- NLK Publikační typ
- závěrečné zprávy o řešení grantu AZV MZ ČR
