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