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Addition of ET(A) receptor blockade increases renoprotection provided by renin-angiotensin system blockade in 5/6 nephrectomized Ren-2 transgenic rats
V. Čertíková Chábová, Z. Vernerová, P. Kujal, Z. Husková, P. Škaroupková, V. Tesař, HJ. Kramer, E. Kompanowska-Jezierska, A. Walkowska, J. Sadowski, L. Červenka, I. Vaněčková,
Language English Country Netherlands
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
NT12171
MZ0
CEP Register
NT14012
MZ0
CEP Register
- MeSH
- Angiotensin II blood MeSH
- Endothelin Receptor Antagonists therapeutic use MeSH
- Endothelin-1 metabolism MeSH
- Cardiomegaly blood complications drug therapy pathology MeSH
- Blood Pressure drug effects MeSH
- Kidney drug effects pathology physiopathology MeSH
- Nephrectomy * MeSH
- Kidney Diseases blood complications drug therapy pathology MeSH
- Protective Agents pharmacology therapeutic use MeSH
- Rats, Sprague-Dawley MeSH
- Rats, Transgenic MeSH
- Receptor, Endothelin A metabolism MeSH
- Renin-Angiotensin System drug effects MeSH
- Renin genetics MeSH
- Systole drug effects MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
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.
Department of Nephrology 1st Faculty of Medicine Charles University Prague Czech Republic
Department of Pathology 3rd Faculty of Medicine Charles University Prague Czech Republic
Institute of Physiology v v i Academy of Sciences of the Czech Republic Prague Czech Republic
Section of Nephrology Medical Policlinic Department of Medicine University of Bonn Bonn Germany
References provided by Crossref.org
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