Combination of chronic kidney disease (CKD) and heart failure (HF) results in extremely high morbidity and mortality. The current guideline-directed medical therapy is rarely effective and new therapeutic approaches are urgently needed. The study was designed to examine if renal denervation (RDN) will exhibit long-standing beneficial effects on the HF- and CKD-related morbidity and mortality. Fawn-hooded hypertensive rats (FHH) served as a genetic model of CKD and fawn-hooded low-pressure rats (FHL) without CKD served as controls. HF was induced by creation of aorto-caval fistula (ACF). RDN was performed 28 days after creation of ACF and the follow-up period was 70 days. ACF FHH subjected to sham-RDN had survival rate of 34 % i.e. significantly lower than 79 % observed in sham-denervated ACF FHL. RDN did not improve the condition and the final survival rate, both in ACF FHL and in ACF FHH. In FHH basal albuminuria was markedly higher than in FHL, and further increased throughout the study. RDN did not lower albuminuria and did not reduce renal glomerular damage in FHH. In these rats creation of ACF resulted in marked bilateral cardiac hypertrophy and alterations of cardiac connexin-43, however, RDN did not modify any of the cardiac parameters. Our present results further support the notion that kidney damage aggravates the HF-related morbidity and mortality. Moreover, it is clear that in the ACF FHH model of combined CKD and HF, RDN does not exhibit any important renoprotective or cardioprotective effects and does not reduce mortality. Key words Chronic kidney disease, Heart failure, Renal denervation, Fawn-hooded hypertensive rats.

• MeSH
• denervace MeSH
• hypertenze * chirurgie   MeSH
• kardiorenální syndrom * etiologie   patofyziologie   MeSH
• krysa rodu rattus MeSH
• ledviny * inervace   MeSH
• modely nemocí na zvířatech MeSH
• srdeční selhání MeSH
• sympatektomie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Renal nerves play a critical role in cardiorenal interactions. Renal denervation (RDN) improved survival in some experimental heart failure (HF) models. It is not known whether these favorable effects are indirect, explainable by a decrease in vascular afterload, or diminished neurohumoral response in the kidneys, or whether RDN procedure per se has direct myocardial effects in the failing heart. To elucidate mechanisms how RDN affects failing heart, we studied load-independent indexes of ventricular function, gene markers of myocardial remodeling, and cardiac sympathetic signaling in HF, induced by chronic volume overload (aorto-caval fistula, ACF) of Ren2 transgenic rats. Volume overload by ACF led to left ventricular (LV) hypertrophy and dysfunction, myocardial remodeling (upregulated Nppa, MYH 7/6 genes), increased renal and circulating norepinephrine (NE), reduced myocardial NE content, increased monoaminoxidase A (MAO-A), ROS production and decreased tyrosine hydroxylase (+) nerve staining. RDN in HF animals decreased congestion in the lungs and the liver, improved load-independent cardiac function (Ees, PRSW, Ees/Ea ratio), without affecting arterial elastance or LV pressure, reduced adverse myocardial remodeling (Myh 7/6, collagen I/III ratio), decreased myocardial MAO-A and inhibited renal neprilysin activity. RDN increased myocardial expression of acetylcholinesterase (Ache) and muscarinic receptors (Chrm2), decreased circulating and renal NE, but increased myocardial NE content, restoring so autonomic control of the heart. These changes likely explain improvements in survival after RDN in this model. The results suggest that RDN has remote, load-independent and favorable intrinsic myocardial effects in the failing heart. RDN therefore could be a useful therapeutic strategy in HF.

• MeSH
• krysa rodu rattus MeSH
• ledviny * inervace   metabolismus   MeSH
• modely nemocí na zvířatech * MeSH
• myokard * metabolismus   MeSH
• noradrenalin * krev   metabolismus   MeSH
• potkani transgenní * MeSH
• remodelace komor fyziologie   MeSH
• srdce inervace   patofyziologie   MeSH
• srdeční selhání * patofyziologie   metabolismus   MeSH
• sympatektomie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• adrenalektomie metody   MeSH
• denervace * metody   MeSH
• hypertenze * farmakoterapie   terapie   MeSH
• klinická studie jako téma MeSH
• ledviny chirurgie   inervace   MeSH
• lidé MeSH
• výběr pacientů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• úvodní články MeSH

Renální sympatická denervace (RDN) je metodou, která zažila svůj vzestup i částečný pád v léčbě farmakologicky nekontrolovatelné arteriální hypertenze a jejíž pevné místo v léčebném schématu tohoto onemocnění nebylo stále ještě definováno. Ovlivnění sympatické aktivity se však nachází v centru zájmu i při léčbě řady dalších kardiovaskulárních onemocnění. Patofyziologicky zcela jistě u chronického srdečního selhání, fibrilace síní, některých komorových arytmií a (do větší či menší míry) u některých dalších onemocnění. Cílem této stati je shrnout současné poznatky o přínosu RDN v léčbě výše zmíněných onemocnění.

Renal sympathetic denervation (RDN) is a method that has experienced its rise and fall in the treatment of pharmacologically-resistant essential arterial hypertension, and its firm indications for the treatment of this disease have not been defined yet. Modification of sympathetic activity, however, is in the centre of attention in the treatment of some other pathological conditions. From the pathophysiologic point of view, it is certainly so in the treatment of heart failure, atrial fibrillation, and some types of ventricular arrhythmias, as well as in the case of some other diseases, to a greater or lesser extent. The aim of this article is to review the present knowledge on the contribution of RDN in the treatment of the above-mentioned diseases.

• MeSH
• denervace metody   MeSH
• hypertenze chirurgie   terapie   MeSH
• kardiovaskulární nemoci chirurgie   etiologie   MeSH
• katetrizační ablace metody   MeSH
• ledviny * inervace   MeSH
• lidé MeSH
• nemoci srdce chirurgie   etiologie   MeSH
• noradrenalin krev   MeSH
• sympatektomie * metody   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy 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

OBJECTIVE: We examined if renal denervation (RDN) attenuates the progression of aortocaval fistula (ACF)-induced heart failure or improves renal hemodynamics in Ren-2 transgenic rats (TGR), a model of angiotensin II (ANG II)-dependent hypertension. METHODS: Bilateral RDN was performed 1 week after creation of ACF. The animals studied were ACF TGR and sham-operated controls, and both groups were subjected to RDN or sham denervation. In separate groups, renal artery blood flow (RBF) responses were determined to intrarenal ANG II (2 and 8 ng), norepinephrine (NE) (20 and 40 ng) and acetylcholine (Ach) (10 and 40 ng) 3 weeks after ACF creation. RESULTS: In nondenervated ACF TGR, the final survival rate was 10 versus 50% in RDN rats. RBF was significantly lower in ACF TGR than in sham-operated TGR (6.2 ± 0.3 vs. 9.7 ± 0.5 mL min-1 g-1, p < 0.05), the levels unaffected by RDN. Both doses of ANG II decreased RBF more in ACF TGR than in sham-operated TGR (-19 ± 3 vs. -9 ± 2% and -47 ± 3 vs. -22 ± 2%, p < 0.05 in both cases). RDN did not alter RBF responses to the lower dose, but increased it to the higher dose of ANG II in sham-operated as well as in ACF TGR. NE comparably decreased RBF in ACF TGR and sham-operated TGR, and RDN increased RBF responsiveness. Intrarenal Ach increased RBF significantly more in ACF TGR than in sham-operated TGR (29 ± 3 vs. 17 ± 3%, p < 0.05), the changes unaffected by RDN. ACF creation induced marked bilateral cardiac hypertrophy and lung congestion, both attenuated by RDN. In sham-operated but not in ACF TGR, RDN significantly decreased mean arterial pressure. CONCLUSION: The results show that RDN significantly improved survival rate in ACF TGR; however, this beneficial effect was not associated with improvement of reduced RBF or with attenuation of exaggerated renal vascular responsiveness to ANG II.

• MeSH
• angiotensin II metabolismus   MeSH
• arteriovenózní píštěl komplikace   MeSH
• hypertenze komplikace   genetika   metabolismus   MeSH
• krysa rodu rattus MeSH
• ledviny inervace   chirurgie   MeSH
• potkani Sprague-Dawley MeSH
• potkani transgenní MeSH
• renin genetika   MeSH
• srdeční selhání komplikace   genetika   metabolismus   terapie   MeSH
• sympatektomie * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

We showed previously that in anaesthetized rats acute noninvasive renal denervation (DNX) induced an increase in arterial blood pressure (MABP), unlike the usual hypotensive effect. Here we aimed to establish the background of such unusual response, especially the role of oxidative stress as suggested by an earlier study. The contribution of oxidative stress was explored by studying the effects on DNX-induced MABP increase of pretreatment with 4-hydroxy-3-methoxyacetophenone (apocynin, APO), a powerful antioxidant and antihypertensive agent, and N(omega)-propyl-L-arginine (L-NPA), a blocker of neuronal nitric oxide synthase (nNOS). In anaesthetized Wistar rats maintained on standard (STD) or high-salt (HS) diet sequential right- and left-side DNX was performed. MABP responses were examined without pretreatment and after APO (20 mg/day on two preceding days) and L-NPA (1 mg/kg/h throughout experiment), given alone or combined. In untreated rats, bilateral DNX increased MABP by 6% on STD and 15% on HS diet (P < 0.01 or less); the difference between MABP responses was highly significant (P = 0.002). In STD rats APO or APO + L-NPA treatment failed to alter post-DNX MABP increases whereas L-NPA alone reversed the response and a significant 7% decrease occurred. In HS rats APO and L-NPA given alone reversed the MABP response and significant decreases of 14% (P = 0.001) and 8% (P = 0.01), were seen. Surprisingly, with L-NPA + APO pretreatment only abolishment (not reversal) of post-DNX pressure increase occurred. The results suggest that both systemic, intrarenal and brain oxidative stress, and excessive nNOS activity, mostly in the brain, determine the unexpected post-DNX pressure increase.

• MeSH
• acetofenony farmakologie   MeSH
• anestezie MeSH
• arginin analogy a deriváty   farmakologie   MeSH
• denervace * MeSH
• krevní tlak * účinky léků   MeSH
• ledviny inervace   MeSH
• oxidační stres * účinky léků   MeSH
• potkani Wistar MeSH
• sodík dietní farmakologie   MeSH
• synthasa oxidu dusnatého, typ I fyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The present paper is an extension to our earlier publication (Šochman et al. 2016) documenting a beneficial effect of renal sympathetic denervation on pharmacologically uncontrollable hypertension in a group of seven patients followed up for 1-2 years post-procedure. The same patients remained on ambulatory follow-up for another 5-6 years, with the beneficial effect persisting throughout the follow-up period while on the same medication.

• MeSH
• antihypertenziva terapeutické užití   MeSH
• hypertenze diagnóza   farmakoterapie   chirurgie   MeSH
• krevní tlak fyziologie   MeSH
• ledviny inervace   fyziologie   chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• senioři MeSH
• sympatektomie trendy   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

To determine the influence of IGF-1 deletion on renal sympathetic nerve activity (RSNA), left ventricular dysfunction, and renal function in deoxycorticosterone acetate (DOCA)-salt hypertensive mice. The DOCA-salt hypertensive mice models were constructed and the experiment was classified into WT (Wild-type mice) +sham, LID (Liver-specific IGF-1 deficient mice) + sham, WT + DOCA, and LID+ DOCA groups. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum IGF-1 levels in mice. The plasma norepinephrine (NE), urine protein, urea nitrogen and creatinine, as well as RSNA were measured. Echocardiography was performed to assess left ventricular dysfunction, and HE staining to observe the pathological changes in renal tissue of mice. DOCA-salt induction time-dependently increased the systolic blood pressure (SBP) of mice, especially in DOCA-salt LID mice. Besides, the serum IGF-1 levels in WT mice were decreased after DOCA-salt induction. In addition, the plasma NE concentration and NE spillover, urinary protein, urea nitrogen, creatinine and RSNA were remarkably elevated with severe left ventricular dysfunction, but the creatinine clearance was reduced in DOCA-salt mice, and these similar changes were obvious in DOCA-salt mice with IGF-1 deletion. Moreover, the DOCA-salt mice had tubular ectasia, glomerular fibrosis, interstitial cell infiltration, and increased arterial wall thickness, and the DOCA-salt LID mice were more serious in those aspects. Deletion of IGF-1 may lead to enhanced RSNA in DOCA-salt hypertensive mice, thereby further aggravating left ventricular dysfunction and renal damage.

• MeSH
• deoxykortikosteron-21-acetát toxicita   MeSH
• dysfunkce levé srdeční komory krev   chemicky indukované   patofyziologie   MeSH
• hypertenze krev   chemicky indukované   patofyziologie   MeSH
• insulinu podobný růstový faktor I nedostatek   genetika   MeSH
• ledviny účinky léků   inervace   fyziologie   MeSH
• mineralokortikoidy toxicita   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• noradrenalin krev   MeSH
• sympatická vlákna postgangliová účinky léků   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Katétrová renální denervace v současné době nepředstavuje rutinní metodu v léčbě arteriální hypertenze. Nejnovější studie svědčí pro možnou efektivitu víceelektrodových systémů ve snižování krevního tlaku v krátkodobém časovém horizontu. Stále ale chybí důkazy, že metoda je ve snižování krevního tlaku účinná dlouhodobě, že snižuje morbiditu nebo mortalitu a že je efektivní s ohledem na náklady spojené se samotnou procedurou.

Catheter-based renal denervation is currently not a routine method in treating arterial hypertension. The most recent studiessuggest possible effectiveness of multi-electrode systems in reducing blood pressure in the short term. However, evidence is stilllacking that the method is effective in reducing blood pressure in the long term as well as that it reduces morbidity or mortalityrates and is cost-effective given the costs associated with the procedure itself.

• MeSH
• antihypertenziva terapeutické užití   MeSH
• denervace * metody   trendy   MeSH
• farmakoterapie metody   trendy   MeSH
• hypertenze maligní * diagnóza   komplikace   terapie   MeSH
• hypertenze diagnóza   etiologie   terapie   MeSH
• katetrizace metody   trendy   MeSH
• ledviny * chirurgie   inervace   MeSH
• lidé MeSH
• metaanalýza jako téma MeSH
• neurochirurgické výkony metody   trendy   MeSH
• statistika jako téma MeSH
• výsledky a postupy - zhodnocení (zdravotní péče) MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH