title: Effects of low-dose spironolactone combined with irbesartan on cardiac hypertrophy induced by pressure overload in rats.
abstract: BACKGROUND
  The mineralocorticoid receptor (MR) blockade in the heart is an attractive therapeutic option for the treatment of heart failure. However, the use of MR antagonist is limited by an increased incidence of hyperkalemia owing to MR blockade in the kidney. This study was designed to evaluate and compare the effectiveness of a low, non-pressure-lowering dose of spironolactone (Sp) with that of a conventional blood pressure-lowering dose combined with irbesartan on pathological cardiac remodeling as well as serum potassium level in pressure-overload rats.
  
  
  METHODS
  The pressure-overloaded myocardial remodelling was produced by partial abdominal aortic constriction (PAAC) in rats. Four weeks after PAAC, animals were respectively treated with vehicle, irbesartan (15 mg/kg) alone, low-dose Sp (1 mg/kg) or conventional-dose of Sp (20 mg/kg) in combination with irbesartan for consecutive four weeks.
  
  
  RESULTS
  The result demonstrated that compared to irbesartan monotherapy, the combination of irbesartan and spironolactone both in low- and conventional-dose exhibited additional cardioprotection against PAAC-induced cardiac remodelling. Low-dose spironolactone was as effective in inhibiting cardiac hypertrophy, fibrosis and in improving diastolic function as high dose. Low-dose spironolactone did not lead to a rise in potassium serum levels, but high dose did.
  
  
  CONCLUSIONS
  This study suggests that combined low dose of spironolactone and irbesartan may be an effective and safety therapeutic strategy for cardiac hypertrophy and heart failure.
authors: The Key Laboratory of Neural and Vascular Biology, Ministry of Education; The Key Laboratory of New Drug Pharmacology and Toxicology Hebei Province, China ; Department of Pharmacology, Hebei Medical University Shijiazhuang 050017, China ; The Fourth Hospital of Hebei Medical University Shijiazhuang 050051, China.
authors: Jingtao
authors: J
authors: Ma
authors: The Key Laboratory of Neural and Vascular Biology, Ministry of Education; The Key Laboratory of New Drug Pharmacology and Toxicology Hebei Province, China ; Department of Pharmacology, Hebei Medical University Shijiazhuang 050017, China.
authors: Hongxue
authors: H
authors: Zhang
authors: Department of Toxicology, Hebei Medical University Shijiazhuang 050017, China.
authors: Huicai
authors: H
authors: Guo
authors: The Key Laboratory of Neural and Vascular Biology, Ministry of Education; The Key Laboratory of New Drug Pharmacology and Toxicology Hebei Province, China ; Department of Pharmacology, Hebei Medical University Shijiazhuang 050017, China.
authors: Yanfang
authors: Y
authors: Xu
keywords: Spironolactone; aldosterone; irbesartan; myocardial remodelling
references: Kidney Int. 2012 Sep;82(6):643-51
references: 22622494
references: Curr Hypertens Rep. 2003 Oct;5(5):408-17
references: 12948434
references: JAMA. 2009 Oct 21;302(15):1658-65
references: 19843900
references: Mol Cell Endocrinol. 2012 Mar 24;350(2):266-72
references: 21784127
references: Hypertension. 2013 Jul;62(1):62-9
references: 23648698
references: Basic Clin Pharmacol Toxicol. 2012 Aug;111(2):75-80
references: 22304485
references: Am J Cardiovasc Dis. 2012;2(1):50-7
references: 22254214
references: Fundam Clin Pharmacol. 2014 Jun;28(3):249-56
references: 23600722
references: Phytother Res. 2014 Jan;28(1):22-7
references: 23553964
references: Compr Physiol. 2014 Jul;4(3):1017-55
references: 24944029
references: J Cardiovasc Pharmacol. 2003 Jun;41(6):830-7
references: 12775959
references: Eur J Clin Invest. 2012 Oct;42(10):1112-20
references: 22536780
references: Am J Physiol. 1997 Oct;273(4 Pt 2):H1824-31
references: 9362249
references: Basic Clin Pharmacol Toxicol. 2006 Dec;99(6):418-24
references: 17169122
references: Circulation. 2005 May 3;111(17):2157-64
references: 15851599
references: N Engl J Med. 1999 Sep 2;341(10):709-17
references: 10471456
references: Postgrad Med J. 2010 Mar;86(1013):136-42
references: 20237007
references: Curr Heart Fail Rep. 2011 Mar;8(1):7-13
references: 21207206
references: Biomed Res Int. 2013;2013:161396
references: 24288663
references: Am J Physiol Heart Circ Physiol. 2011 Apr;300(4):H1484-91
references: 21239636
references: Circ Cardiovasc Genet. 2013 Aug;6(4):381-90
references: 23852419
references: Am J Physiol Endocrinol Metab. 2008 Jul;295(1):E103-9
references: 18460596
references: Clin Exp Hypertens. 2011;33(7):427-36
references: 21777149
references: Vasc Health Risk Manag. 2013;9:321-31
references: 23836977
references: Am J Physiol Heart Circ Physiol. 2005 Sep;289(3):H1131-6
references: 15863455
references: QJM. 2012 Nov;105(11):1049-57
references: 22723454
references: Am J Cardiol. 2013 Nov 1;112(9):1427-32
references: 24035170
references: Hypertens Res. 2011 Jul;34(7):817-24
references: 21471977
references: Pharmazie. 2014 May;69(5):374-8
references: 24855831
references: Clin Exp Pharmacol Physiol. 2009 Nov;36(11):1110-9
references: 19413592
references: J Cardiovasc Pharmacol. 2006 Dec;48(6):265-73
references: 17204904
references: Circulation. 2002 Aug 27;106(9):1055-7
references: 12196328
references: Heart. 2001 Apr;85(4):E8
references: 11250985
references: Clin Nephrol. 2009 Dec;72(6):449-56
references: 19954722