Title:

Addition of ETA receptor blockade increases renoprotecion provided by renin-angiotensin system blockade in5/6 nephrectomized

Creator:

Certikova-Chabova, Vera ; Vernerova, Zdenka ; Kujal, Peter ; Huskova, Zdenka ; Skaroupkova, Petra ; Tesal, Vladimir ; Kramer, Hubert J. ; Kompanowska-Jezierska, Elżbieta ; Walkowska, Agnieszka ; Sadowski, Janusz ; Cervenka, Ludek ; Vaneckova, Ivana

Contributor:

Department of Nephrology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic ; artment of Renal and Body Fluid Physiology, M. Mossakowski Medical Research Centre, Polish Academy of Science, Warsaw, Poland of Institute of Physiology , Academy of Sciences of the Czech Republic, Prague

Publisher:

Elsevier

Place of publishing:

Amsterdam

Date issued/created:

2014

Type of object:

Journal/Article

Subject and Keywords:

Hypertension; Chronic kidney disease; Endothelin receptor type A; 5/6 nephrectomy; End-organ damage

Abstract:

MS: There is evidence that in addition to hypertension and hyperactivity of the renin-angiotensin system (RAS), enhanced intrarenal activity of endothelin (ET) system contributes to the pathophysiology and progression of chronic kidney disease (CKD). This prompted us to examine if this progression would be alleviated by addition of type A ET receptor (ETA) blockade to the standard blockade of RAS.MAIN METHODS: Ren-2 transgenic rats (TGR) after 5/6 renal ablation (5/6 NX) served as a model of CKD. For RAS inhibition a combination of angiotensin-converting enzyme inhibitor (trandolapril, 6 mg/L drinking water) and angiotensin II type 1 receptor blocker (losartan, 100 mg/L drinking water) was used. Alternatively, ETA receptor blocker (atrasentan, 5 mg·kg(-1)·day(-1) in drinking water) was added to the combined RAS blockade. The follow-up period was 44 weeks after 5/6 NX, and the rats' survival rate, systolic blood pressure (SBP), proteinuria and indices of renal glomerular damage were evaluated.KEY FINDINGS: The survival rate was at first improved, by either therapeutic regime, however, the efficiency of RAS blockade alone considerably decreased 36 weeks after 5/6 NX: final survival rate of 65% was significantly lower than 91% achieved with combined RAS and ETA receptor blockade. SBP was not affected by the addition of ETA blockade while proteinuria and renal glomerular damage were further reduced.

Relation:

Life Sciences

Volume:

118

Issue:

2

Start page:

297

End page:

305

Resource type:

Text

Detailed Resource Type:

Article

Format:

text/xml

Language:

eng

Language of abstract:

eng

Rights:

Creative Commons Attribution BY-NC-SA 3.0 PL license

Terms of use:

Copyright-protected material. [CC BY-NC-SA 3.0 PL] May be used within the scope specified in Creative Commons Attribution BY-NC-SA 3.0 PL license, full text available at: ; -

Digitizing institution:

Mossakowski Medical Research Institute PAS

Original in:

Library of the Mossakowski Medical Research Institute PAS

Projects co-financed by:

Programme Innovative Economy, 2010-2014, Priority Axis 2. R&D infrastructure

Access:

Open