Jingtao Ma1, Hongxue Zhang2, Huicai Guo3, Yanfang Xu2. 1. 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. 2. 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. 3. Department of Toxicology, Hebei Medical University Shijiazhuang 050017, China.
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.
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: Nicolas Vignier; Philippe Le Corvoisier; Charlotte Blard; Lucien Sambin; Feriel Azibani; Saskia Schlossarek; Claude Delcayre; Lucie Carrier; Luc Hittinger; Jin Bo Su Journal: Fundam Clin Pharmacol Date: 2013-04-18 Impact factor: 2.748
Authors: Nancy M Albert; Clyde W Yancy; Li Liang; Xin Zhao; Adrian F Hernandez; Eric D Peterson; Christopher P Cannon; Gregg C Fonarow Journal: JAMA Date: 2009-10-21 Impact factor: 56.272
Authors: James M Luther; Pengcheng Luo; Zuofei Wang; Samuel E Cohen; Hyung-Suk Kim; Agnes B Fogo; Nancy J Brown Journal: Kidney Int Date: 2012-05-23 Impact factor: 10.612