Combined Inhibition of Soluble Epoxide Hydrolase and Renin-Angiotensin System Exhibits Superior Renoprotection to Renin-Angiotensin System Blockade in 5/6 Nephrectomized Ren-2 Transgenic Hypertensive Rats with Established Chronic Kidney Disease

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F18%3A10376090" target="_blank" >RIV/00216208:11110/18:10376090 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11120/18:43916439 RIV/00216208:11130/18:10376090 RIV/00023001:_____/18:00076971

Result on the web

<a href="https://doi.org/10.1159/000487902" target="_blank" >https://doi.org/10.1159/000487902</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1159/000487902" target="_blank" >10.1159/000487902</a>

Result language

angličtina

Original language name

Combined Inhibition of Soluble Epoxide Hydrolase and Renin-Angiotensin System Exhibits Superior Renoprotection to Renin-Angiotensin System Blockade in 5/6 Nephrectomized Ren-2 Transgenic Hypertensive Rats with Established Chronic Kidney Disease

Original language description

Background/Aims: We found recently that increasing renal epoxyeicosatrienoic acids (EETs) levels by blocking soluble epoxide hydrolase (sEH), an enzyme responsible for EETs degradation, shows renoprotective actions and retards the progression of chronic kidney disease (CKD) in Ren-2 transgenic hypertensive rats (TGR) after 5/6 renal ablation (5/6 NX). This prompted us to examine if additional protection is provided when sEH inhibitor is added to the standard renin-angiotensin system (RAS) blockade, specifically in rats with established CKD. Methods: For RAS blockade, an angiotensin-converting enzyme inhibitor along with an angiotensin II type receptor blocker was used. RAS blockade was compared to sEH inhibition added to the RAS blockade. Treatments were initiated 6 weeks after 5/6 NX in TGR and the follow-up period was 60 weeks. Results: Combined RAS and sEH blockade exhibited additional positive impact on the rat survival rate, further reduced albuminuria, further reduced glomerular and tubulointerstitial injury, and attenuated the decline in creatinine clearance when compared to 5/6 NX TGR subjected to RAS blockade alone. These additional beneficial actions were associated with normalization of the intrarenal EETs deficient and a further reduction of urinary angiotensinogen excretion. Conclusion: This study provides evidence that addition of pharmacological inhibition of sEH to RAS blockade in 5/6 NX TGR enhances renoprotection and retards progression of CKD, notably, when applied at an advanced stage.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30217 - Urology and nephrology

Project

<a href="/en/project/NV15-28671A" target="_blank" >NV15-28671A: Pharmacological blockade of both the endothelin system and soluble epoxyde hydrolase as a new aproach to the treatment of hypertensive organ damage</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2018

Confidentiality

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

Name of the periodical

Kidney &amp; Blood Pressure Research

ISSN

1420-4096

e-ISSN

—

Volume of the periodical

43

Issue of the periodical within the volume

2

Country of publishing house

CH - SWITZERLAND

Number of pages

21

Pages from-to

329-349

UT code for WoS article

000434716500004

EID of the result in the Scopus database

2-s2.0-85050997694