The aim was to evaluate the effects of renal denervation (RDN) on autoregulation of renal hemodynamics and the pressure-natriuresis relationship in Ren-2 transgenic rats (TGR) with aorto-caval fistula (ACF)-induced heart failure (HF). RDN was performed one week after creation of ACF or sham-operation. Animals were prepared for evaluation of autoregulatory capacity of renal blood flow (RBF) and glomerular filtration rate (GFR), and of the pressure-natriuresis characteristics after stepwise changes in renal arterial pressure (RAP) induced by aortic clamping. Their basal values of blood pressure and renal function were significantly lower than with innervated sham-operated TGR (p < 0.05 in all cases): mean arterial pressure (MAP) (115 ± 2 vs. 160 ± 3 mmHg), RBF (6.91 ± 0.33 vs. 10.87 ± 0.38 ml.min-1.g-1), urine flow (UF) (11.3 ± 1.79 vs. 43.17 ± 3.24 μl.min-1.g-1) and absolute sodium excretion (UNaV) (1.08 ± 0.27 vs, 6.38 ± 0.76 μmol.min-1.g-1). After denervation ACF TGR showed improved autoregulation of RBF: at lowest RAP level (80 mmHg) the value was higher than in innervated ACF TGR (6.92 ± 0.26 vs. 4.54 ± 0.22 ml.min-1.g-1, p < 0.05). Also, the pressure-natriuresis relationship was markedly improved after RDN: at the RAP of 80 mmHg UF equaled 4.31 ± 0.99 vs. 0.26 ± 0.09 μl.min-1.g-1 recorded in innervated ACF TGR, UNaV was 0.31 ± 0.05 vs. 0.04 ± 0.01 μmol min-1.g-1 (p < 0.05 in all cases). In conclusion, in our model of hypertensive rat with ACF-induced HF, RDN improved autoregulatory capacity of RBF and the pressure-natriuresis relationship when measured at the stage of HF decompensation.

• MeSH
• hodnoty glomerulární filtrace MeSH
• hypertenze * MeSH
• kardiorenální syndrom * MeSH
• krevní tlak MeSH
• krysa rodu rattus MeSH
• ledviny MeSH
• natriuréza MeSH
• píštěle * MeSH
• potkani transgenní MeSH
• renální oběh MeSH
• srdeční selhání * MeSH
• sympatektomie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The aim of the present study was to assess the autoregulatory capacity of renal blood flow (RBF) and of the pressure-natriuresis characteristics in the early phase of heart failure (HF) in rats, normotensive and with angiotensin II (ANG II)-dependent hypertension. Ren-2 transgenic rats (TGR) were employed as a model of ANG II-dependent hypertension. HF was induced by creating the aorto-caval fistula (ACF). One week after ACF creation or sham-operation, the animals were prepared for studies evaluating in vivo RBF autoregulatory capacity and the pressure-natriuresis characteristics after stepwise changes in renal arterial pressure (RAP) induced by aortic clamping. In ACF TGR the basal mean arterial pressure, RBF, urine flow (UF), and absolute sodium excretion (UNaV) were all significantly lower tha n in sham-operated TGR. In the latter, reductions in renal arterial pressure (RAP) significantly decreased RBF whereas in ACF TGR they did not change. Stepwise reductions in RAP resulted in marked decreases in UF and UNaV in sham-operated as well as in ACF TGR, however, these decreases were significantly greater in the former. Our data show that compared with sham-operated TGR, ACF TGR displayed well-maintained RBF autoregulatory capacity and improved slope of the pressure-natriuresis relationship. Thus, even though in the very early HF stage renal dysfunction was demonstrable, in the HF model of ANG II-dependent hypertensive rat such dysfunction and the subsequent HF decompensation cannot be simply ascribed to impaired renal autoregulation and pressure-natriuresis relationship.

• MeSH
• angiotensin II farmakologie   MeSH
• homeostáza MeSH
• hypertenze * MeSH
• krevní tlak MeSH
• krysa rodu rattus MeSH
• ledviny MeSH
• natriuréza MeSH
• potkani transgenní MeSH
• renální oběh MeSH
• sodík MeSH
• srdeční selhání * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Aldosterone regulates blood pressure (BP) through water and sodium balance. In our study, we studied if continuous treatment with a mineralocorticoid receptor antagonist, spironolactone (30 mg/kg/day) for 20 days can: 1) attenuate hypertension development and restore inverted 24-h BP rhythm in hypertensive transgenic (mRen-2)27 rats (TGR) measured by telemetry; 2) improve function of the kidneys and heart; 3) be protective against high salt load (1% in water) by mitigating oxidative injury and improving kidney function. Spironolactone decreased albuminuria and 8-isoprostane in normal and salt load conditions in BP-independent effects. Salt load increased BP, impaired autonomic balance, suppressed plasma aldosterone level and increased natriuresis, albuminuria and oxidative injury in TGR. Spironolactone did not restore the inverted 24-h rhythm of BP in TGR, therefore, mineralocorticoids are not crucial in regulation of BP daily profile. Spironolactone improved kidney function, decreased oxidative stress and was protective against high salt load in the BP-independent manner.

• MeSH
• albuminurie MeSH
• aldosteron * farmakologie   MeSH
• antagonisté mineralokortikoidních receptorů farmakologie   MeSH
• geneticky modifikovaná zvířata MeSH
• hypertenze * MeSH
• krevní tlak MeSH
• krysa rodu rattus MeSH
• ledviny MeSH
• receptory mineralokortikoidů genetika   MeSH
• spironolakton farmakologie   MeSH
• voda farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Nefrotický syndrom (NS) je charakterizován velkou proteinurií (nad 3,5 g/24 h), hypalbuminemií, generalizovanými otoky, hyperlipidemií a poruchami koagulace. Vedle primárních glomerulonefritid se vyskytuje u sekundárních glomerulopatií při diabetu, amyloidóze, systémových zánětlivých chorobách, onkologických onemocněních, u poškození léky a drogami, při alergiích, závažných infekcích a u dětí jsou i formy vrozené. Nejčastější příčinou NS v dospělosti je diabetes mellitus (DM). V současnosti je DM příčinou 40 % selhání ledvin u nemocných na dialýze. Z hlediska prevence je proto věnována velká pozornost gliflozinům (SGLT2 inhibitory), které mají prokazatelně nefroprotektivní účinky. Glifloziny vedou k navození glyko- surie, doprovázené současně natriurézou a osmotickou diurézou. Účinnost gliflozinů na snížení glykemie je proporcionální k úrovni glomerulární filtrace, zatímco efekty vázané na natriurézu jsou zachovány ve všech stadiích renální insuficience.

Nephrotic syndrome (NS) is characterized by high proteinuria (over 3,5g/24 hrs), hypalbuminaemia, general edemas and hypercoagulation. Beside of primary glomerulonephritides this is found in secundary glomerulopaties eg. diabetes, systemic inflammatory diseases, oncology, damage by drugs and poisoning, by alergy, serious infections and in children from hereditary reasons. The most frequent reason for NS in adults patiens is diabetes and diabetes with nephropathy represents almost 40% of dialysed patiens. From this point of view, there is great interest focusing on gliflozins (SGLT2 inhibitors) with positive nephroprotecive effect. It leads do increasing of glycosuria with concomitant natriuresis and osmotic diuresis. The effect is proportional to glomerulal filtration, but the effect on natriuresis stay in all stages of renal insufficiency.

• MeSH
• diabetes mellitus MeSH
• diabetické nefropatie diagnóza   farmakoterapie   prevence a kontrola   MeSH
• glifloziny aplikace a dávkování   terapeutické užití   MeSH
• hypoproteinemie diagnóza   etiologie   MeSH
• lidé MeSH
• metabolismus MeSH
• multimorbidita MeSH
• nefrotický syndrom * diagnóza   etiologie   terapie   MeSH
• proteinurie diagnóza   etiologie   patofyziologie   MeSH
• Check Tag
• lidé MeSH

• MeSH
• cévní endotel účinky léků   MeSH
• diabetes mellitus farmakoterapie   MeSH
• diabetické nefropatie prevence a kontrola   MeSH
• glukagonu podobný peptid 1 * farmakologie   terapeutické užití   MeSH
• hmotnostní úbytek účinky léků   MeSH
• inhibitory dipeptidylpeptidasy 4 * farmakologie   terapeutické užití   MeSH
• krevní tlak účinky léků   MeSH
• ledviny * účinky léků   MeSH
• lidé MeSH
• natriuréza účinky léků   MeSH
• oxidační stres účinky léků   MeSH
• Check Tag
• lidé MeSH

OBJECTIVES: The global morbidity and mortality related to hypertension and associated disorders increases continuously and novel therapeutic strategies are still in high demand. Increasing evidence suggests the important role in blood pressure regulation of cytochrome P-450-dependent metabolites of arachidonic acid. Epoxyeicosatrienoic acids (EETs) induce vasodilation and natriuresis, and have renoprotective and anti-inflammatory properties. 20-HETE is an arachidonic acid metabolite with both prohypertensive and antihypertensive activities. To explore the pathophysiological role of arachidonic acid metabolites in more detail, we examined the antihypertensive efficiency of EET-A, a stable analog of 14,15-EET, and of AAA, a novel antagonist of the 20-HETE receptors. METHODS: Male spontaneously hypertensive rats (SHR) were treated for 5 weeks with EET-A, AAA or the combination; age-matched untreated SHR and normotensive Wistar-Kyoto rats served as controls. EET-A and AAA were administered in drinking water at 10 mg/kg/day each. SBP was measured by telemetry and urine, blood, and tissue samples were collected for relevant analyses. RESULTS: EET-A or AAA given alone had no significant effect on SHR blood pressure. In contrast, combined treatment with AAA and EET-A was significantly antihypertensive, causing a decrease in SBP from 180 ± 3 to 160 ± 5 mmHg (P < 0.05). Additionally, the combined treatment attenuated cardiac hypertrophy, decreased kidney ANG II level, increased natriuresis, and increased the excretion of nitric oxide metabolites. CONCLUSION: Considering the beneficial impact of the combined treatment with EET-A and AAA on SHR blood pressure and cardiovascular and renal function, we suggest that the treatment is a promising therapeutic strategy for human hypertension.

• MeSH
• antihypertenziva farmakologie   MeSH
• hypertenze metabolismus   MeSH
• ikosanoidy farmakologie   MeSH
• krevní tlak účinky léků   MeSH
• krysa rodu rattus MeSH
• kyseliny hydroxyeikosatetraenové antagonisté a inhibitory   MeSH
• potkani inbrední SHR MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

B-type natriuretic peptide (BNP) exhibits roles in natriuresis and diuresis, making it an ideal drug that may aid in diuresing a fluid-overloaded patient with poor or worsening renal function. Several randomized clinical trials have tested the hypothesis that infusions of pharmacological doses of BNP to acute heart failure (HF) patients may enhance decongestion and preserve renal function in this clinical setting. Unfortunately, none of these have demonstrated beneficial outcomes. The current challenge for BNP research in acute HF lies in addressing a failure of concept and a reluctance to abandon an ineffective research model. Future success will necessitate a detailed understanding of the mechanism of action of BNP, as well as better integration of basic and clinical science.

• MeSH
• akutní nemoc MeSH
• lidé MeSH
• natriuretický peptid typu B farmakologie   terapeutické užití   MeSH
• srdeční selhání farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

High-salt intake is one of the major dietary determinants of increased blood pressure and cardiovascular disease. Thus, there is scientific and medical interest in understanding the mechanistic abnormalities mediating the pressor effects of salt (salt sensitivity). According to historical theory, salt sensitivity stems from an impairment in renal function (referred to as "abnormal pressure natriuresis" or a "natriuretic handicap"), which causes salt-sensitive subjects to excrete a sodium load more slowly, and retain more of it than salt-resistant normotensive controls. However, this historical view has come under intense scrutiny because of growing awareness that in salt-sensitive subjects, acute salt loading does not usually induce greater increases in sodium balance and cardiac output than those induced by salt loading in salt-resistant normotensive controls. Here we highlight pioneering studies from Japan that challenge the historical thinking and provide insights into a contemporary theory of salt sensitivity termed the "vasodysfunction theory." According to this theory, initiation of salt-induced hypertension usually involves abnormal vascular resistance responses to increased salt intake, not greater renal retention of a salt load in salt-sensitive subjects than in normal subjects. By shifting the focus from the historical theory to a contemporary final common pathway for the pathogenesis of salt sensitivity, research from Japan is building the scientific foundation for more effective approaches to the prevention and treatment of salt-induced hypertension. Among the most promising approaches are dietary strategies for reducing the risk for salt-induced hypertension that do not depend on reducing salt consumption in the population.

• MeSH
• arginin analogy a deriváty   metabolismus   MeSH
• cévní rezistence * MeSH
• dieta MeSH
• hypertenze etiologie   prevence a kontrola   MeSH
• kuchyňská sůl škodlivé účinky   MeSH
• lidé MeSH
• oxid dusnatý metabolismus   MeSH
• renální oběh * MeSH
• sodík moč   MeSH
• solný stres MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH

In 2011 Fujita and coworkers proposed that ß-adrenergic stimulation causes decreased serine/threonine-protein kinase WNK4 transcription leading to the activation of Na-Cl cotransporter (NCC) which participates in salt sensitivity and salt hypertension development in rodents. The aim of our study was to investigate whether the above hypothesis is also valid for salt hypertension of Dahl rats, which are characterized by high sympathetic tone and abnormal renal sodium handling. Male 8-week-old salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) Dahl rats were fed either low-salt diet (LS, 0.4 % NaCl) or high-salt diet (HS, 4 % NaCl) for 6 weeks. Half of the animals on either diet were chronically treated with non-selective ß-blocker propranolol (100 mg/kg/day). At the end of the experiment diuresis and sodium excretion were measured prior and after hydrochlorothiazide injection (HCTZ, 10 mg/kg i.p.). Furthermore, blood pressure (BP), heart rate (HR), sympathetic (pentolinium 5 mg/kg i.v.) and NO-dependent (L-NAME 30 mg/kg i.v.) BP components were determined. Chronic HS diet feeding increased BP through sympathoexcitation in SS/Jr but not in SR/Jr rats. Concomitant propranolol treatment did not lower BP in either experimental group. Under the conditions of low salt intake HCTZ increased diuresis, natriuresis and fractional sodium excretion in SR/Jr but not in SS/Jr rats. HS diet feeding attenuated renal response to HCT in SR/Jr rats, whereas no HCTZ effect was observed in SS/Jr rats fed HS diet. Propranolol treatment did not modify diuresis or natriuresis in any experimental group. In conclusions, our present data do not support the idea on the essential importance of renal ß-adrenergic-WNK4-NCC pathway in pathogenesis and/or maintenance of salt hypertension in Dahl rats.

• MeSH
• beta blokátory terapeutické užití   MeSH
• hypertenze chemicky indukované   farmakoterapie   metabolismus   MeSH
• krevní tlak účinky léků   fyziologie   MeSH
• krysa rodu rattus MeSH
• kuchyňská sůl aplikace a dávkování   škodlivé účinky   MeSH
• potkani inbrední Dahl MeSH
• propranolol farmakologie   terapeutické užití   MeSH
• protein-serin-threoninkinasy metabolismus   MeSH
• rodina nosičů rozpuštěných látek 12, člen 1 metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• chronická renální insuficience farmakoterapie   metabolismus   patofyziologie   MeSH
• diabetes mellitus 2. typu farmakoterapie   MeSH
• diabetické nefropatie patofyziologie   MeSH
• glifloziny MeSH
• glomerulus patofyziologie   MeSH
• hemodynamika účinky léků   MeSH
• hypoglykemika farmakologie   terapeutické užití   MeSH
• krevní glukóza metabolismus   účinky léků   MeSH
• krevní tlak MeSH
• lidé MeSH
• natriuréza MeSH
• proximální tubuly ledvin patofyziologie   MeSH
• sodík metabolismus   MeSH
• transportér 2 pro sodík a glukózu MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH