Title:

Addition of ETA receptor blockade increases renoprotection provided by renin–angiotensin system blockade in 5/6 nephrectomized Ren-2 transgenic rats

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 ; Department of Pathology, 3rd Faculty of Medicine, Charles University, Prague, Czech Republicc Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republicd Section of Nephrology, Medical Policlinic, Department of Medicine, University of Bonn, Bonn, Germanye Department of Renal and Body Fluid Physiology, M. Mossakowski Medical Research Centre, Polish Academy of Science, Warsaw, Polandf Institute of Physiology v.v.i., Academy of Sciences of the Czech Republic, Prague

Publisher:

Elsevier

Place of publishing:

Amsterdam

Date issued/created:

2014

Type of object:

Czasopismo/Artykuł

Subject and Keywords:

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

Abstract:

AIMS: 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.SIGNIFICANCE: Our data show that a combined RAS and ETA receptor blockade exhibits additional beneficial effects on survival rate and the progression of CKD in 5/6 NX TGR, as compared with RAS inhibition alone.

Relation:

Life Sciences

Volume:

118

Issue:

2

Start page:

297

End page:

305

Resource type:

Tekst

Detailed Resource Type:

Artykuł

Format:

text/xml

Language:

eng

Language of abstract:

eng

Rights:

Licencja Creative Commons Uznanie autorstwa-Użycie niekomercyjne-Na tych samych warunkach 3.0 Polska

Terms of use:

Zasób chroniony prawem autorskim. [CC BY-NC-SA 3.0 PL] Korzystanie dozwolone zgodnie z licencją Creative Commons Uznanie autorstwa-Użycie niekomercyjne-Na tych samych warunkach 3.0 Polska, której pełne postanowienia dostępne są pod adresem: ; -

Digitizing institution:

Instytut Medycyny Doświadczalnej i Klinicznej im. M. Mossakowskiego Polskiej Akademii Nauk

Original in:

Biblioteka Instytutu Medycyny Doświadczalnej i Klinicznej im. M. Mossakowskiego PAN

Projects co-financed by:

Program Operacyjny Innowacyjna Gospodarka, lata 2010-2014, Priorytet 2. Infrastruktura strefy B + R

Access:

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