Addition of ETA receptor blockade increases renoprotection provided by renin–angiotensin system blockade in 5/6 nephrectomized Ren-2 transgenic rats
PBN-AR
Instytucja
Instytut Medycyny Doświadczalnej i Klinicznej im. Mirosława Mossakowskiego Polskiej Akademii Nauk
Źródłowe zdarzenia ewaluacyjne
Informacje podstawowe
Główny język publikacji
en
Czasopismo
LIFE SCIENCES
ISSN
0024-3205
EISSN
Wydawca
PERGAMON-ELSEVIER SCIENCE LTD
DOI
URL
Rok publikacji
2014
Numer zeszytu
2
Strony od-do
297-305
Numer tomu
118
Identyfikator DOI
Liczba arkuszy
0,70
Słowa kluczowe
en
Hypertension
Chronic kidney disease
Endothelin receptor type A
5/6 nephrectomy
End-organ damage
Streszczenia
Język
en
Treść
Aims: There is evidence that in addition to hypertension and hyperactivity of the renin–angiotensin system (RAS), enhanced intrarenal activity of endothelin (ET) systemcontributes 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.
Cechy publikacji
ORIGINAL_ARTICLE
Inne
System-identifier
599516
CrossrefMetadata from Crossref logo
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