A Novel Aldosterone Antagonist Limits Renal Injury in 5/6 Nephrectomy
Carregando...
Citações na Scopus
13
Tipo de produção
article
Data de publicação
2017
Título da Revista
ISSN da Revista
Título do Volume
Editora
NATURE PUBLISHING GROUP
Autores
KOWALA, M. C.
BREYER, M. D.
JADHAV, P. K.
MONTROSE-RAFIZADEH, Chahrzad
Citação
SCIENTIFIC REPORTS, v.7, article ID 7899, 12p, 2017
Resumo
Aldosterone antagonists slow the progression of chronic kidney disease (CKD), but their use is limited by hyperkalemia, especially when associated with RAS inhibitors. We examined the renoprotective effects of Ly, a novel non-steroidal mineralocorticoid receptor (MR) blocker, through two experimental protocols: In Protocol 1, male Munich-Wistar rats underwent 5/6 renal ablation (Nx), being divided into: Nx+V, receiving vehicle, Nx+Eple, given eplerenone, 150 mg/kg/day, and Nx+Ly, given Ly, 20 mg/kg/day. A group of untreated sham-operated rats was also studied. Ly markedly raised plasma renin activity (PRA) and aldosterone, and exerted more effective anti-albuminuric and renoprotective action than eplerenone. In Protocol 2, Nx rats remained untreated until Day 60, when they were divided into: Nx+V receiving vehicle; Nx+L treated with losartan, 50 mg/kg/day; Nx+L+Eple, given losartan and eplerenone, and Nx+L+Ly, given losartan and Ly. Treatments lasted for 90 days. As an add-on to losartan, Ly normalized blood pressure and albuminuria, and prevented CKD progression more effectively than eplerenone. This effect was associated with strong stimulation of PRA and aldosterone. Despite exhibiting higher affinity for the MR than either eplerenone or spironolactone, Ly caused no hyperkalemia. Ly may become a novel asset in the effort to detain the progression of CKD.
Palavras-chave
Referências
- Arias SCA, 2016, AM J PHYSIOL-RENAL, V310, pF135, DOI 10.1152/ajprenal.00388.2015
- Arias SCA, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0056215
- Aldigier JC, 2005, J AM SOC NEPHROL, V16, P3306, DOI 10.1681/asn.2004090804
- ALNEMRI ES, 1991, J BIOL CHEM, V266, P18072
- Bakris GL, 2015, JAMA-J AM MED ASSOC, V314, P884, DOI 10.1001/jama.2015.10081
- Beasley TM, 1995, J EXP EDUC, V64, P79
- Bianchi S, 2015, INT J CARDIOL, V200, P20, DOI 10.1016/j.ijcard.2015.05.125
- BINART N, 1991, P NATL ACAD SCI USA, V88, P10681, DOI 10.1073/pnas.88.23.10681
- Brenner BM, 2001, NEW ENGL J MED, V345, P861, DOI 10.1056/NEJMoa011161
- Brown NJ, 2013, NAT REV NEPHROL, V9, P459, DOI 10.1038/nrneph.2013.110
- Chen H, 2013, KIDNEY BLOOD PRESS R, V37, P557, DOI 10.1159/000355736
- CHENG Y, 1973, BIOCHEM PHARMACOL, V22, P3099
- Fujihara CK, 2000, J AM SOC NEPHROL, V11, P283
- Fujihara CK, 2007, AM J PHYSIOL-RENAL, V292, pF1810, DOI 10.1152/ajprenal.00521.2006
- Fujisaki K, 2014, HYPERTENS RES, V37, P993, DOI 10.1038/hr.2014.110
- GUYTON AC, 1991, SCIENCE, V252, P1813, DOI 10.1126/science.2063193
- Haller H, 2016, CURR HYPERTENS REP, V18, DOI 10.1007/s11906-016-0649-2
- Ikeda H, 2009, KIDNEY INT, V75, P147, DOI 10.1038/ki.2008.507
- JEPSEN FL, 1979, VIRCHOWS ARCH A, V383, P265, DOI 10.1007/BF00430245
- Joyeux A, 1997, ANAL BIOCHEM, V249, P119, DOI 10.1006/abio.1997.2147
- Kim HY, 2014, KIDNEY BLOOD PRESS R, V39, P573, DOI 10.1159/000368470
- Kolkhof P, 2015, CURR OPIN NEPHROL HY, V24, P417, DOI 10.1097/MNH.0000000000000147
- Lewis EJ, 2001, NEW ENGL J MED, V345, P851, DOI 10.1056/NEJMoa011303
- Meyers MJ, 2010, J MED CHEM, V53, P5979, DOI 10.1021/jm100505n
- Nagai Y, 2005, HYPERTENSION, V46, P1039, DOI 10.1161/01.HYP.0000174593.88899.68
- Nagase M, 2006, J AM SOC NEPHROL, V17, P3438, DOI 10.1681/ASN.2006080944
- Nemeth Z, 2009, NEPHROL DIAL TRANSPL, V24, P3640, DOI 10.1093/ndt/gfp371
- Nielsen SE, 2012, DIABETIC MED, V29, pE184, DOI 10.1111/j.1464-5491.2012.03585.x
- Piecha G, 2008, AM J PHYSIOL-RENAL, V295, pF137, DOI 10.1152/ajprenal.00065.2008
- Pitt B, 2013, EUR HEART J, V34, P2453, DOI 10.1093/eurheartj/eht187
- Rodriguez-Iturbe B, 2002, AM J PHYSIOL-RENAL, V282, pF191
- Schjoedt KJ, 2005, KIDNEY INT, V68, P2829, DOI 10.1111/j.1523-1755.2005.00756.x
- Schrier RW, 2010, NAT REV NEPHROL, V6, P61, DOI 10.1038/nrneph.2009.228
- Spat A, 2004, MOL CELL ENDOCRINOL, V217, P23, DOI 10.1016/j.mce.2003.10.046
- Tait JF, 1999, CLIN EXP PHARMACOL P, V26, P947, DOI 10.1046/j.1440-1681.1999.03173.x
- WALLENSTEIN S, 1980, CIRC RES, V47, P1
Coleções
Artigos e Materiais de Revistas Científicas - FM/MPT
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - FM/MCP
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/13
Carregar mais Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - FM/MCP
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/13