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
Language English Country Great Britain, England Media print-electronic
Document type Journal Article
- Keywords
- 5/6 nephrectomy, Chronic kidney disease, endothelin system, hypertension, renin–angiotensin system,
- MeSH
- Albuminuria MeSH
- Angiotensins drug effects metabolism MeSH
- Endothelin A Receptor Antagonists pharmacology MeSH
- Atrasentan MeSH
- Angiotensin II Type 1 Receptor Blockers pharmacology MeSH
- Renal Insufficiency, Chronic metabolism MeSH
- Glomerular Filtration Rate drug effects MeSH
- Hypertension MeSH
- Indoles pharmacology MeSH
- Angiotensin-Converting Enzyme Inhibitors pharmacology MeSH
- Cardiomegaly MeSH
- Drug Therapy, Combination MeSH
- Creatinine metabolism MeSH
- Blood Pressure drug effects MeSH
- Rats MeSH
- Kidney drug effects metabolism MeSH
- Losartan pharmacology MeSH
- Survival Rate MeSH
- Nephrectomy MeSH
- Rats, Sprague-Dawley MeSH
- Rats, Transgenic MeSH
- Disease Progression MeSH
- Pyrrolidines pharmacology MeSH
- Receptor, Endothelin A drug effects metabolism MeSH
- Receptor, Endothelin B drug effects metabolism MeSH
- Renin-Angiotensin System drug effects MeSH
- Renin drug effects metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Angiotensins MeSH
- Endothelin A Receptor Antagonists MeSH
- Atrasentan MeSH
- Angiotensin II Type 1 Receptor Blockers MeSH
- Indoles MeSH
- Angiotensin-Converting Enzyme Inhibitors MeSH
- Creatinine MeSH
- Losartan MeSH
- Pyrrolidines MeSH
- Receptor, Endothelin A MeSH
- Receptor, Endothelin B MeSH
- Renin MeSH
- trandolapril MeSH Browser
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
References provided by Crossref.org
Altered Balance between Vasoconstrictor and Vasodilator Systems in Experimental Hypertension
