Renoprotection Provided by Additional Diuretic Treatment in Partially Nephrectomized Ren-2 Transgenic Rats Subjected to the Combined RAS and ETA Blockade
Autor: | Hana Rauchová, Luděk Červenka, S Hojná, Zdeňka Vaňourková, Ivana Vaněčková, Michaela Kadlecová, Elzbieta Kompanowska-Jezierska, Josef Zicha, Zdenka Vernerová |
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Rok vydání: | 2019 |
Předmět: |
losartan
Physiology medicine.medical_treatment 030232 urology & nephrology Renal function 030204 cardiovascular system & hematology Pharmacology lcsh:Physiology renoprotection 03 medical and health sciences 0302 clinical medicine Physiology (medical) nephrectomy medicine trandolapril Original Research lcsh:QP1-981 biology atrasentan business.industry Atrasentan Glomerulosclerosis Angiotensin-converting enzyme medicine.disease hydrochlorothiazide Blockade Losartan biology.protein Diuretic business chronic kidney disease medicine.drug Kidney disease |
Zdroj: | Frontiers in Physiology Frontiers in Physiology, Vol 10 (2019) |
ISSN: | 1664-042X |
Popis: | Objective: Our previous study in heterozygous Ren-2 transgenic rats (TGR) demonstrated that long-term treatment with endothelin receptor A (ETA) blocker atrasentan added to the renin-angiotensin system (RAS) blockade had renoprotective effects in a model of chronic kidney disease induced by partial nephrectomy. Since ETA blockade is known to cause edema, we were interested whether diuretic treatment added to this therapy would be beneficial. Design and Methods: Partial nephrectomy (NX) was performed at the age of 3 months in TGR rats which were subjected to: i) RAS blockade alone (angiotensin receptor blocker losartan and angiotensin converting enzyme inhibitor trandolapril), ii) combined RAS (losartan and trandolapril) and ETA receptor blockade (atrasentan), or iii) diuretic (hydrochlorothiazide) added to the combined RAS+ETA blockade for 50 weeks following NX. Results: At the end of the study systolic blood pressure and cardiac hypertrophy were similarly decreased in all treated groups. Survival was significantly improved by ETA receptor blockade added to RAS blockade with no further effects of diuretic treatment. However, additional diuretic treatment combined with RAS+ETA blockade decreased body weight and had beneficial renoprotective effects – reductions of both kidney weight and kidney damage markers. Proteinuria gradually increased in rats treated with RAS blockade alone, while it was substantially lowered by additional ETA blockade. In rats treated with additional diuretic, proteinuria was progressively reduced throughout the experiment. Conclusions: A diuretic added to the combined RAS and ETA blockade has late renoprotective effects in chronic kidney disease induced by partial nephrectomy in Ren-2 transgenic rats. The diuretic improved: renal function (evaluated as proteinuria and creatinine clearance), renal morphology (kidney mass, glomerular volume), and histological markers of kidney damage (glomerulosclerosis index, tubulointerstitial injury). |
Databáze: | OpenAIRE |
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