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

BACKGROUND: Hyperkalemia (HK) is associated with suboptimal renin-angiotensin system (RAS) inhibitor and mineralocorticoid receptor antagonist (MRA) use in heart failure with reduced ejection fraction (HFrEF). OBJECTIVES: This study sought to assess characteristics and RAS inhibitor/MRA use in patients receiving patiromer during the DIAMOND (Patiromer for the Management of Hyperkalemia in Subjects Receiving RAASi Medications for the Treatment of Heart Failure) run-in phase. METHODS: Patients with HFrEF and HK or past HK entered a run-in phase of ≤12 weeks with patiromer-facilitated RAS inhibitor/MRA optimization to achieve ≥50% recommended RAS inhibitor dose, 50 mg/d MRA, and normokalemia. Patients achieving these criteria (randomized group) were compared with the run-in failure group (patients not meeting the randomization criteria). RESULTS: Of 1,038 patients completing the run-in, 878 (84.6%) were randomized and 160 (15.4%) were run-in failures. Overall, 422 (40.7%) had HK entering run-in with a similar frequency in the randomized and run-in failure groups (40.3% vs 42.5%; P = 0.605). From start to the end of run-in, in the randomized group, an increase was observed in target RAS inhibitor and MRA use in patients with HK (RAS inhibitor: 76.8% to 98.6%; MRA: 35.9% to 98.6%) and past HK (RAS inhibitor: 60.5% to 98.1%; MRA: 15.6% to 98.7%). Despite not meeting the randomization criteria, an increase after run-in was observed in the run-in failure group in target RAS inhibitor (52.5% to 70.6%) and MRA use (15.0% to 48.1%). This increase was observed in patients with HK (RAS inhibitor: 51.5% to 64.7%; MRA: 19.1% to 39.7%) and past HK (RAS inhibitor: 53.3% to 75.0%; MRA: 12.0% to 54.3%). CONCLUSIONS: In patients with HFrEF and HK or past HK receiving suboptimal RAS inhibitor/MRA therapy, RAS inhibitor/MRA optimization increased during patiromer-facilitated run-in.

• Klíčová slova
• heart failure, hyperkalemia, mineralocorticoid receptor antagonists, patiromer, renin–angiotensin system inhibitors,
• MeSH
• antagonisté mineralokortikoidních receptorů * terapeutické užití   MeSH
• antagonisté receptorů pro angiotenzin terapeutické užití   MeSH
• hyperkalemie * farmakoterapie   krev   MeSH
• inhibitory ACE terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• polymery * terapeutické užití   MeSH
• renin-angiotensin systém účinky léků   MeSH
• senioři MeSH
• srdeční selhání * farmakoterapie   MeSH
• tepový objem účinky léků   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antagonisté mineralokortikoidních receptorů * MeSH
• antagonisté receptorů pro angiotenzin MeSH
• inhibitory ACE MeSH
• patiromer MeSH Prohlížeč
• polymery * MeSH

The aim of the present study was to perform kidney messenger ribonucleic acid (mRNA) analysis in normotensive, Hannover Sprague-Dawley (HanSD) rats and hypertensive, Ren-2 renin transgenic rats (TGR) after doxorubicin-induced heart failure (HF) with specific focus on genes that are implicated in the pathophysiology of HF-associated cardiorenal syndrome. We found that in both strains renin and angiotensin-converting enzyme mRNA expressions were upregulated indicating that the vasoconstrictor axis of the renin-angiotensin system was activated. We found that pre-proendothelin-1, endothelin-converting enzyme type 1 and endothelin type A receptor mRNA expressions were upregulated in HanSD rats, but not in TGR, suggesting the activation of endothelin system in HanSD rats, but not in TGR. We found that mRNA expression of cytochrome P-450 subfamily 2C23 was downregulated in TGR and not in HanSD rats, suggesting the deficiency in the intrarenal cytochrome P450-dependent pathway of arachidonic acid metabolism in TGR. These results should be the basis for future studies evaluating the pathophysiology of cardiorenal syndrome secondary to chemotherapy-induced HF in order to potentially develop new therapeutic approaches.

• Klíčová slova
• chemotherapy-induced heart failure, cytochrome P-450, doxorubicin, endothelin system, hypertension, kidney, renal adrenergic system, renin-angiotensin-aldosterone system,
• MeSH
• doxorubicin škodlivé účinky   MeSH
• hypertenze komplikace   genetika   patofyziologie   MeSH
• krysa rodu Rattus MeSH
• ledviny účinky léků   patofyziologie   MeSH
• messenger RNA genetika   MeSH
• nemoci ledvin chemicky indukované   genetika   patofyziologie   MeSH
• potkani Sprague-Dawley MeSH
• potkani transgenní MeSH
• protinádorová antibiotika škodlivé účinky   MeSH
• regulace genové exprese účinky léků   MeSH
• renin-angiotensin systém účinky léků   MeSH
• renin genetika   MeSH
• srdeční selhání chemicky indukované   genetika   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• doxorubicin MeSH
• messenger RNA MeSH
• protinádorová antibiotika MeSH
• Ren2 protein, rat MeSH Prohlížeč
• renin MeSH

BACKGROUND: Preclinical studies suggested that pharmacological inhibition of the renin-angiotensin-aldosterone system (RAAS) by ACE inhibitors (ACEis) or angiotensin II receptor blockers (ARBs) may increase local angiotensin-converting enzyme 2 (ACE2) expression. METHODS: In this study, we evaluated the effect of ACEi or ARB treatment on expression of ACE2, ACE, and AGTR1 in 3-month protocol kidney allograft biopsies of stable patients using RT-qPCR (n = 48). Protein ACE2 expression was assessed using immunohistochemistry from paraffin sections. RESULTS: The therapy with RAAS blockers was not associated with increased ACE2, ACE, or ATGR1 expression in kidney allografts and also ACE2 protein immunohistochemistry did not reveal differences among groups. CONCLUSIONS: ACEis or ARBs in kidney transplant recipients do not affect local ACE2 expression. This observation supports long-term RAAS treatment in kidney transplant recipients, despite acute complications such as COVID-19 where ACE2 serves as the entry protein for infection.

• Klíčová slova
• Angiotensin-converting enzyme 2, COVID-19, Kidney, Renin-angiotensin system inhibitors,
• MeSH
• alografty účinky léků   metabolismus   MeSH
• angiotensin-konvertující enzym 2 analýza   antagonisté a inhibitory   genetika   MeSH
• antagonisté receptorů pro angiotenzin farmakologie   terapeutické užití   MeSH
• antihypertenziva farmakologie   terapeutické užití   MeSH
• COVID-19 komplikace   genetika   MeSH
• dospělí MeSH
• exprese genu účinky léků   MeSH
• ledviny účinky léků   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA analýza   genetika   MeSH
• renin-angiotensin systém účinky léků   MeSH
• senioři MeSH
• transplantace ledvin MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ACE2 protein, human MeSH Prohlížeč
• angiotensin-konvertující enzym 2 MeSH
• antagonisté receptorů pro angiotenzin MeSH
• antihypertenziva MeSH
• messenger RNA MeSH

The renin angiotensin system (RAS) regulates fluid balance, blood pressure and maintains vascular tone. The potent vasoconstrictor angiotensin II (Ang II) produced by angiotensin-converting enzyme (ACE) comprises the classical RAS. The non-classical RAS involves the conversion of Ang II via ACE2 into the vasodilator Ang (1-7) to counterbalance the effects of Ang II. Furthermore, ACE2 converts AngA into another vasodilator named alamandine. The over activation of the classical RAS (increased vasoconstriction) and depletion of the non-classical RAS (decreased vasodilation) results in vascular dysfunction. Vascular dysfunction is the leading cause of atherosclerosis and cardiovascular disease (CVD). Additionally, local RAS is expressed in various tissues and regulates cellular functions. RAS dysregulation is involved in other several diseases such as inflammation, renal dysfunction and even cancer growth. An approach in restoring vascular dysfunction and other pathological diseases is to either increase the activity of ACE2 or reduce the effect of the classical RAS by counterbalancing Ang II effects. The antitrypanosomal agent, diminazene aceturate (DIZE), is one approach in activating ACE2. DIZE has been shown to exert beneficial effects in CVD experimental models of hypertension, myocardial infarction, type 1 diabetes and atherosclerosis. Thus, this review focuses on DIZE and its effect in several tissues such as blood vessels, cardiac, renal, immune and cancer cells.

• Klíčová slova
• angiotensin-converting enzyme II, cardiovascular disease, diminazene aceturate, endothelial dysfunction, renin angiotensin system,
• MeSH
• aktivace enzymů MeSH
• aktivátory enzymů škodlivé účinky   terapeutické užití   MeSH
• angiotensin-konvertující enzym 2 metabolismus   MeSH
• diminazen škodlivé účinky   analogy a deriváty   terapeutické užití   MeSH
• kardiovaskulární nemoci farmakoterapie   enzymologie   patofyziologie   MeSH
• lidé MeSH
• nádory farmakoterapie   enzymologie   patofyziologie   MeSH
• renin-angiotensin systém účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• ACE2 protein, human MeSH Prohlížeč
• aktivátory enzymů MeSH
• angiotensin-konvertující enzym 2 MeSH
• diminazen MeSH
• diminazene aceturate MeSH Prohlížeč

INTRODUCTION: Previous studies in Ren-2 transgenic hypertensive rats (TGR) after 5/6 renal ablation (5/6 NX) have shown that besides pharmacological blockade of the renin-angiotensin system (RAS) also increasing kidney tissue epoxyeicosatrienoic acids (EET) levels by blocking soluble epoxide hydrolase (sEH), an enzyme responsible for degradation of EETs, and endothelin type A (ETA) receptor blockade retards chronic kidney disease (CKD) progression. This prompted us to evaluate if this progression will be alleviated by the addition of sEH inhibitor and ETA receptor antagonist to the standard complex blockade of RAS (angiotensin-converting enzyme inhibitor plus angiotensin II type 1 receptor blocker) in rats with established CKD. METHODS: The treatment regimens were initiated 6 weeks after 5/6 NX in TGR, and the follow-up period was 60 weeks. RESULTS: The addition of sEH inhibition to RAS blockade improved survival rate, further reduced albuminuria and renal glomerular and kidney tubulointerstitial injury, and attenuated the decline in creatinine clearance - all this as compared with 5/6 NX TGR treated with RAS blockade alone. Addition of ETA receptor antagonist to the combined RAS and sEH blockade not only offered no additional renoprotection but, surprisingly, also abolished the beneficial effects of adding sEH inhibitor to the RAS blockade. CONCLUSION: These data indicate that pharmacological strategies that combine the blockade of RAS and sEH could be a novel tool to combat the progression of CKD. Any attempts to further extend this therapeutic regimen should be made with extreme caution.

• Klíčová slova
• 5/6 Renal mass reduction, Chronic kidney disease, Endothelin A receptor blocker, Hypertension, Renin-angiotensin system, Soluble epoxide hydrolase inhibitor,
• MeSH
• antagonisté endotelinového receptoru A farmakologie   MeSH
• chronická renální insuficience prevence a kontrola   MeSH
• epoxid hydrolasy antagonisté a inhibitory   MeSH
• hypertenze MeSH
• krysa rodu Rattus MeSH
• nefrektomie MeSH
• potkani transgenní MeSH
• receptor endotelinu A MeSH
• renin-angiotensin systém účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antagonisté endotelinového receptoru A MeSH
• epoxid hydrolasy MeSH
• receptor endotelinu A MeSH

Our previous studies demonstrated that chronic systemic blockade of renin-angiotensin system (RAS) lowered blood pressure (BP) of Ren-2 transgenic rats (TGR) by the attenuation of both angiotensin II-dependent and sympathetic vasoconstriction. Since systemic RAS blockade also inhibits brain RAS, we were interested which effects on these two types of vasoconstriction will have the central RAS blockade in hypertensive TGR rats. Adult male heterozygous TGR rats and their Hannover Sprague Dawley (HanSD) controls were subjected to chronic systemic or intracerebroventricular administration of either angiotensin type 1 receptor blocker losartan or direct renin inhibitor aliskiren for 4 weeks. Additional groups of TGR and HanSD rats were used for the evaluation of acute peripheral and brain effects of angiotensin II. Both chronic systemic and intracerebroventricular administrations of losartan or aliskiren normalized BP of TGR animals. BP effect of brain RAS blockade was based solely on the reduced sympathetic vasoconstriction, while systemic RAS blockade attenuated both angiotensin II-dependent and sympathetic vasoconstriction. Surprisingly, neither peripheral nor central pressor effects of acute angiotensin II administration were enhanced in TGR compared to HanSD rats. In conclusion, sympathoinhibition represents the main mechanism of BP reduction in heterozygous TGR rats subjected to chronic brain or systemic RAS blockade, while peripheral attenuation of angiotensin II-dependent vasoconstriction during systemic RAS blockade is less important. Our data suggest that the participation of angiotensin II in BP control of adult heterozygous TGR rats is shifted from peripheral vasoconstriction to central sympathoexcitation. Similar mechanisms cannot be excluded in human essential hypertension.

• Klíčová slova
• Aliskiren, Angiotensin II, Hypertension, Intracerebroventricular, Losartan,
• MeSH
• angiotensin II aplikace a dávkování   farmakologie   MeSH
• blokátory receptorů AT1 pro angiotensin II farmakologie   MeSH
• heterozygot MeSH
• injekce intraventrikulární MeSH
• krevní tlak účinky léků   MeSH
• mozek patologie   MeSH
• oxid dusnatý metabolismus   MeSH
• potkani Sprague-Dawley MeSH
• potkani transgenní MeSH
• receptor angiotensinu typ 1 metabolismus   MeSH
• renin-angiotensin systém účinky léků   MeSH
• srdce účinky léků   MeSH
• sympatický nervový systém účinky léků   MeSH
• vazokonstrikce účinky léků   MeSH
• velikost orgánu účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• angiotensin II MeSH
• blokátory receptorů AT1 pro angiotensin II MeSH
• oxid dusnatý MeSH
• receptor angiotensinu typ 1 MeSH

Basal calcium sensitization is decreased in spontaneously hypertensive rats, although their blood pressure (BP) response to acute Rho-kinase inhibition is enhanced. Using fasudil (Rho-kinase inhibitor) or nifedipine (L-VDCC blocker), we evaluated the contribution of calcium sensitization and calcium entry to BP maintenance in hypertensive transgenic Ren-2 rats (TGR) focusing on the influence of major vasoactive systems and/or baroreflex efficiency on BP responses to these two drugs. Homozygous TGR and normotensive Hannover Sprague-Dawley (HanSD) control rats aged 5, 11, or 22 weeks were used. The acute BP-lowering effects of fasudil or nifedipine were studied in intact rats, nitric oxide-deficient L-NAME-pretreated rats and rats subjected to combined blockade of the renin-angiotensin system (RAS), sympathetic nervous system (SNS) and nitric oxide synthase (NOS). Fasudil- or nifedipine-induced BP reduction increased during hypertension development in TGR. By contrast, the nifedipine-induced BP response decreased, whereas the fasudil-induced BP response increased with age in HanSD controls. Our data indicated a major contribution of nifedipine-sensitive calcium entry and relative attenuation of calcium sensitization in hypertensive rats compared with normotensive controls. The BP responses to fasudil or nifedipine were enhanced by NOS inhibition and combined blockade in normotensive HanSD rats but not in hypertensive TGR. In conclusion, calcium sensitization is attenuated by endogenous nitric oxide in normotensive HanSD rats but not in hypertensive TGR. Moreover, BP reduction elicited by acute Rho-kinase inhibition is partially compensated by enhanced sympathetic vasoconstriction. The decreased compensation in hypertensive rats with impaired baroreflex efficiency explains their greater BP response to fasudil than in normotensive animals.

• Klíčová slova
• Calcium sensitization, L type voltage-dependent calcium channels, RhoA/Rho kinase pathway, calcium entry, fasudil, nifedipine, nitric oxide,
• MeSH
• 1-(5-isochinolinsulfonyl)-2-methylpiperazin analogy a deriváty   farmakologie   MeSH
• baroreflex účinky léků   fyziologie   MeSH
• blokátory kalciových kanálů farmakologie   MeSH
• hypertenze patofyziologie   MeSH
• krevní tlak účinky léků   fyziologie   MeSH
• krysa rodu Rattus MeSH
• nifedipin farmakologie   MeSH
• potkani Sprague-Dawley MeSH
• potkani transgenní MeSH
• renin-angiotensin systém účinky léků   MeSH
• vazokonstrikce účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1-(5-isochinolinsulfonyl)-2-methylpiperazin MeSH
• blokátory kalciových kanálů MeSH
• fasudil MeSH Prohlížeč
• nifedipin MeSH

Ivabradine, the selective inhibitor of the If current in the sinoatrial node, exerts cardiovascular protection by its bradycardic effect and potentially pleiotropic actions. However, there is a shortage of data regarding ivabradine's interaction with the renin-angiotensin-aldosterone system (RAAS). This study investigated whether ivabradine is able to protect a hypertensive heart in the model of L-NAME-induced hypertension and to interfere with the RAAS. Four groups (n = 10/group) of adult male Wistar rats were treated as follows for four weeks: control, ivabradine (10 mg/kg/day), L-NAME (40 mg/kg/day), and L-NAME plus ivabradine. L-NAME administration increased systolic blood pressure (SBP) and left ventricular (LV) weight, enhanced hydroxyproline concentration in the LV, and deteriorated the systolic and diastolic LV function. Ivabradine reduced heart rate (HR) and SBP, and improved the LV function. The serum concentrations of angiotensin Ang 1⁻8 (Ang II), Ang 1⁻5, Ang 1⁻7, Ang 1⁻10, Ang 2⁻8, and Ang 3⁻8 were decreased in the L-NAME group and ivabradine did not modify them. The serum concentration of aldosterone and the aldosterone/Ang II ratio were enhanced by L-NAME and ivabradine reduced these changes. We conclude that ivabradine improved the LV function of the hypertensive heart in L-NAME-induced hypertension. The protective effect of ivabradine might have been associated with the reduction of the aldosterone level.

• Klíčová slova
• L-NAME, aldosterone, angiotensin II, fibrosis, heart function, hypertension, ivabradine,
• MeSH
• aldosteron krev   MeSH
• angiotensiny krev   MeSH
• biologické markery MeSH
• echokardiografie MeSH
• funkce levé komory srdeční účinky léků   MeSH
• hydroxyprolin krev   metabolismus   MeSH
• hypertenze diagnóza   etiologie   metabolismus   patofyziologie   MeSH
• ivabradin farmakologie   MeSH
• kardiovaskulární látky farmakologie   MeSH
• kolagen metabolismus   MeSH
• krevní tlak účinky léků   MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech MeSH
• NG-nitroargininmethylester škodlivé účinky   MeSH
• renin-angiotensin systém účinky léků   MeSH
• renin krev   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aldosteron MeSH
• angiotensiny MeSH
• biologické markery MeSH
• hydroxyprolin MeSH
• ivabradin MeSH
• kardiovaskulární látky MeSH
• kolagen MeSH
• NG-nitroargininmethylester MeSH
• renin MeSH

Chronic kidney disease (CKD) is a life-threatening disease arising as a frequent complication of diabetes, obesity and hypertension. Since it is typically undetected for long periods, it often progresses to end-stage renal disease. CKD is characterized by the development of progressive glomerulosclerosis, interstitial fibrosis and tubular atrophy along with a decreased glomerular filtration rate. This is associated with podocyte injury and a progressive rise in proteinuria. As endothelin-1 (ET-1) through the activation of endothelin receptor type A (ET(A)) promotes renal cell injury, inflammation, and fibrosis which finally lead to proteinuria, it is not surprising that ET(A) receptors antagonists have been proven to have beneficial renoprotective effects in both experimental and clinical studies in diabetic and non-diabetic CKD. Unfortunately, fluid retention encountered in large clinical trials in diabetic CKD led to the termination of these studies. Therefore, several advances, including the synthesis of new antagonists with enhanced pharmacological activity, the use of lower doses of ET antagonists, the addition of diuretics, plus simply searching for distinct pathological states to be treated, are promising targets for future experimental studies. In support of these approaches, our group demonstrated in adult subtotally nephrectomized Ren-2 transgenic rats that the addition of a diuretic on top of renin-angiotensin and ET(A) blockade led to a further decrease of proteinuria. This effect was independent of blood pressure which was normalized in all treated groups. Recent data in non-diabetic CKD, therefore, indicate a new potential for ET(A) antagonists, at least under certain pathological conditions.

• MeSH
• antagonisté endotelinového receptoru A farmakologie   terapeutické užití   MeSH
• antihypertenziva farmakologie   terapeutické užití   MeSH
• chronická renální insuficience metabolismus   prevence a kontrola   MeSH
• diuretika farmakologie   terapeutické užití   MeSH
• endotelin-1 antagonisté a inhibitory   metabolismus   MeSH
• hypertenze farmakoterapie   metabolismus   MeSH
• lidé MeSH
• receptor endotelinu A metabolismus   MeSH
• renin-angiotensin systém účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antagonisté endotelinového receptoru A MeSH
• antihypertenziva MeSH
• diuretika MeSH
• endotelin-1 MeSH
• receptor endotelinu A MeSH