title: Renin-angiotensin system blockade alone or combined with ETAreceptor blockade: effects on the course of chronic kidney disease in 5/6 nephrectomized Ren-2 transgenic hypertensive rats.
abstract: 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 ETAblockade 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, ETAreceptor 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 ETAreceptor 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 ETAreceptor 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.
authors.affiliation: a Center for Experimental Medicine, Institute for Clinical and Experimental Medicine , Prague , Czech Republic.|b Department of Physiology, Faculty of Science , Charles University , Prague , Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Sedláková
authors.affiliation: c Department of Nephrology, 1st Faculty of Medicine , Charles University , Prague , Czech Republic.
authors.forename: Věra
authors.initials: V
authors.lastname: Čertíková Chábová
authors.affiliation: a Center for Experimental Medicine, Institute for Clinical and Experimental Medicine , Prague , Czech Republic.|b Department of Physiology, Faculty of Science , Charles University , Prague , Czech Republic.
authors.forename: Šárka
authors.initials: Š
authors.lastname: Doleželová
authors.affiliation: a Center for Experimental Medicine, Institute for Clinical and Experimental Medicine , Prague , Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Škaroupková
authors.affiliation: a Center for Experimental Medicine, Institute for Clinical and Experimental Medicine , Prague , Czech Republic.
authors.forename: Libor
authors.initials: L
authors.lastname: Kopkan
authors.affiliation: a Center for Experimental Medicine, Institute for Clinical and Experimental Medicine , Prague , Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Husková
authors.affiliation: a Center for Experimental Medicine, Institute for Clinical and Experimental Medicine , Prague , Czech Republic.|f Department of Pathology, 3rd Faculty of Medicine , Charles University , Prague , Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Červenková
authors.affiliation: a Center for Experimental Medicine, Institute for Clinical and Experimental Medicine , Prague , Czech Republic.
authors.forename: Soňa
authors.initials: S
authors.lastname: Kikerlová
authors.affiliation: d Institute of Physiology, v.v.i., Academy of Sciences of the Czech Republic , Prague , Czech Republic.
authors.forename: Ivana
authors.initials: I
authors.lastname: Vaněčková
authors.affiliation: e Department of Renal and Body Fluid Physiology , Mossakowski Medical Research Center, Polish Academy of Sciences , Warsaw , Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Sadowski
authors.affiliation: e Department of Renal and Body Fluid Physiology , Mossakowski Medical Research Center, Polish Academy of Sciences , Warsaw , Poland.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Kompanowska-Jezierska
authors.affiliation: a Center for Experimental Medicine, Institute for Clinical and Experimental Medicine , Prague , Czech Republic.|f Department of Pathology, 3rd Faculty of Medicine , Charles University , Prague , Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Kujal
authors.affiliation: g Section of Nephrology, Medical Policlinic, Department of Medicine , University of Bonn , Bonn , Germany.
authors.forename: Herbert J
authors.initials: HJ
authors.lastname: Kramer
authors.affiliation: a Center for Experimental Medicine, Institute for Clinical and Experimental Medicine , Prague , Czech Republic.|h Department of Pathophysiology, 2nd Faculty of Medicine , Charles University , Prague , Czech Republic.
authors.forename: Luděk
authors.initials: L
authors.lastname: Červenka
mesh_terms: D000419:Albuminuria; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000809:Angiotensins / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000077868:Atrasentan; D001794:Blood Pressure / Q000187:drug effects*; D006332:Cardiomegaly; D003404:Creatinine / Q000378:metabolism; D018450:Disease Progression; D004359:Drug Therapy, Combination; D065130:Endothelin A Receptor Antagonists / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006973:Hypertension; D007211:Indoles / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009392:Nephrectomy; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D044022:Receptor, Endothelin A / Q000187:drug effects / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000187:drug effects / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000378:metabolism*; D012083:Renin / Q000187:drug effects / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects*; D015996:Survival Rate
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000809:Angiotensins; D065130:Endothelin A Receptor Antagonists; D007211:Indoles; D011759:Pyrrolidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C052035:trandolapril; D003404:Creatinine; D012083:Renin; D019808:Losartan; D000077868:Atrasentan
keywords: 5/6 nephrectomy; Chronic kidney disease; endothelin system; hypertension; renin–angiotensin system