Mineralocorticoid receptor antagonism and aldosterone synthesis inhibition do not improve glomerulosclerosis and renal interstitial fibrosis in a model of chronic kidney allograft injury
| Autor: | Konrad Stock, Rob J.J. Hermans, Tobias Lahmer, Marcus Baumann, Christoph Schmaderer, Jens Lutz, Jianxing Chang, Uwe Heemann |
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| Rok vydání: | 2011 |
| Předmět: |
Aldosterone synthase
Male medicine.medical_specialty Kidney Glomerulus Pathogenesis chemistry.chemical_compound Mineralocorticoid receptor Internal medicine medicine Animals Transplantation Homologous Aldosterone Chronic allograft injury Fadrozole Spironolactone Mineralocorticoid Receptor Antagonists Kidney biology business.industry Glomerulosclerosis Focal Segmental Graft Survival Glomerulosclerosis Extracellular Fluid General Medicine medicine.disease Fibrosis Kidney Transplantation Rats Inbred F344 ddc Rats Disease Models Animal medicine.anatomical_structure Endocrinology chemistry Nephrology Rats Inbred Lew biology.protein Cardiology and Cardiovascular Medicine business medicine.drug |
| Zdroj: | Kidneyblood pressure research. 35(6) |
| ISSN: | 1423-0143 |
| Popis: | Chronic allograft injury (CAI) is a major cause of late graft failure with a multifactorial pathogenesis; however, in different experiments an inhibition of the renin-angiotensin system by angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers ameliorated the progression of chronic renal disease. Different concepts supposed that aldosterone is involved in development and/or progression of renal diseases via interaction with a non-epithelial mineralocorticoid receptor (MR), e.g. reducing neointima formation. Our examinations therefore targeted on the effects of the aldosterone synthase inhibitor fadrozole and the MR antagonist spironolactone compared to vehicle in an established rat model of CAI. In our model of CAI, neither the aldosterone biosynthesis inhibitor nor a direct MR blockade had a positive effect on renal CAI in rats. Fadrozole- and spironolactone-treated animals demonstrated a higher proteinuria value, pathologically elevated potassium values, higher tubulointerstitial damage and markedly increased heart weight/body weight as compared to vehicle. Our observations also suggest that inhibition of the MR or the biosynthesis itself had a bad influence on the amount of sclerotic glomeruli and tubulointerstitial damage. The positive effects of inhibition of aldosterone as described in cardiac models could not yet be detected in kidney recipients. |
| Databáze: | OpenAIRE |
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