Renin-angiotensin system blockade alone or combined with ETA receptor blockade: effects on the course of chronic kidney disease in 5/6 nephrectomized Ren-2 transgenic hypertensive rats
Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic
Typ dokumentu časopisecké články
- Klíčová slova
- 5/6 nephrectomy, Chronic kidney disease, endothelin system, hypertension, renin–angiotensin system,
- MeSH
- albuminurie MeSH
- angiotensiny účinky léků metabolismus MeSH
- antagonisté endotelinového receptoru A farmakologie MeSH
- atrasentan MeSH
- blokátory receptorů AT1 pro angiotensin II farmakologie MeSH
- chronická renální insuficience metabolismus MeSH
- hodnoty glomerulární filtrace účinky léků MeSH
- hypertenze MeSH
- indoly farmakologie MeSH
- inhibitory ACE farmakologie MeSH
- kardiomegalie MeSH
- kombinovaná farmakoterapie MeSH
- kreatinin metabolismus MeSH
- krevní tlak účinky léků MeSH
- krysa rodu Rattus MeSH
- ledviny účinky léků metabolismus MeSH
- losartan farmakologie MeSH
- míra přežití MeSH
- nefrektomie MeSH
- potkani Sprague-Dawley MeSH
- potkani transgenní MeSH
- progrese nemoci MeSH
- pyrrolidiny farmakologie MeSH
- receptor endotelinu A účinky léků metabolismus MeSH
- receptor endotelinu B účinky léků metabolismus MeSH
- renin-angiotensin systém účinky léků MeSH
- renin účinky léků metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- angiotensiny MeSH
- antagonisté endotelinového receptoru A MeSH
- atrasentan MeSH
- blokátory receptorů AT1 pro angiotensin II MeSH
- indoly MeSH
- inhibitory ACE MeSH
- kreatinin MeSH
- losartan MeSH
- pyrrolidiny MeSH
- receptor endotelinu A MeSH
- receptor endotelinu B MeSH
- renin MeSH
- trandolapril MeSH Prohlížeč
BACKGROUND: Early addition of endothelin (ET) type A (ETA) receptor blockade to complex renin-angiotensin system (RAS) blockade has previously been shown to provide better renoprotection against progression of chronic kidney disease (CKD) in Ren-2 transgenic hypertensive rats (TGR) after 5/6 renal ablation (5/6 NX). In this study, we examined if additional protection is provided when ETA blockade is applied in rats with already developed CKD. METHODS: For complex RAS inhibition, an angiotensin-converting enzyme inhibitor along with angiotensin II type 1 receptor blocker was used. Alternatively, ETA receptor blocker was added to the RAS blockade. The treatments were initiated 6 weeks after 5/6 NX and the follow-up period was 50 weeks. RESULTS: When applied in established CKD, addition of ETA receptor blockade to the complex RAS blockade brought no further improvement of the survival rate (30% in both groups); surprisingly, aggravated albuminuria (588 ± 47 vs. 245 ± 38 mg/24 h, p < 0.05) did not reduce renal glomerular injury index (1.25 ± 0.29 vs. 1.44 ± 0.26), did not prevent the decrease in creatinine clearance (203 ± 21 vs. 253 ± 17 µl/min/100 g body weight), and did not attenuate cardiac hypertrophy to a greater extent than observed in 5/6 NX TGR treated with complex RAS blockade alone. CONCLUSIONS: When applied in the advanced phase of CKD, addition of ETA receptor blockade to the complex RAS blockade brings no further beneficial renoprotective effects on the CKD progression in 5/6 NX TGR, in addition to those seen with RAS blockade alone.
b Department of Physiology Faculty of Science Charles University Prague Czech Republic
c Department of Nephrology 1st Faculty of Medicine Charles University Prague Czech Republic
f Department of Pathology 3rd Faculty of Medicine Charles University Prague Czech Republic
g Section of Nephrology Medical Policlinic Department of Medicine University of Bonn Bonn Germany
h Department of Pathophysiology 2nd Faculty of Medicine Charles University Prague Czech Republic
Institute of Physiology v v i Academy of Sciences of the Czech Republic Prague Czech Republic
Citace poskytuje Crossref.org
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