Addition of Endothelin A-Receptor Blockade Spoils the Beneficial Effect of Combined Renin-Angiotensin and Soluble Epoxide Hydrolase Inhibition: Studies on the Course of Chronic Kidney Disease in 5/6 Nephrectomized Ren-2 Transgenic Hypertensive Rats

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F19%3A00518671" target="_blank" >RIV/67985823:_____/19:00518671 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11120/19:43919362 RIV/00216208:11130/19:10402368 RIV/00023001:_____/19:00078735 RIV/00216208:11110/19:10402368

Výsledek na webu

<a href="https://doi.org/10.1159/000504137" target="_blank" >https://doi.org/10.1159/000504137</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1159/000504137" target="_blank" >10.1159/000504137</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Addition of Endothelin A-Receptor Blockade Spoils the Beneficial Effect of Combined Renin-Angiotensin and Soluble Epoxide Hydrolase Inhibition: Studies on the Course of Chronic Kidney Disease in 5/6 Nephrectomized Ren-2 Transgenic Hypertensive Rats

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Addition of Endothelin A-Receptor Blockade Spoils the Beneficial Effect of Combined Renin-Angiotensin and Soluble Epoxide Hydrolase Inhibition: Studies on the Course of Chronic Kidney Disease in 5/6 Nephrectomized Ren-2 Transgenic Hypertensive Rats

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30201 - Cardiac and Cardiovascular systems

Projekt

<a href="/cs/project/NV15-28671A" target="_blank" >NV15-28671A: Farmakologická blokáda endotelinového systému a solubilní epoxid hydrolázy jako nový přístup k léčbě hypertenzního orgánového poškození.</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Kidney & Blood Pressure Research

ISSN

1420-4096

e-ISSN

—

Svazek periodika

44

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

13

Strana od-do

1493-1505

Kód UT WoS článku

000505184700017

EID výsledku v databázi Scopus

2-s2.0-85075787703