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Angiotensin receptor‐blockade improves the net balance of cardiac and skeletal muscle calcium handling protein expression and restores cardiac function in heart failure
Author(s) -
Ferreira Julio Cesar Batista,
Pereira Marcelo,
Bueno Carlos Roberto,
Mattos Katt Coelho,
Coelho Marcele,
Krieger Jose Eduardo,
Brum Patricia Chakur
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.966.3
Subject(s) - losartan , medicine , endocrinology , cardiac function curve , heart failure , angiotensin ii , cardiomyopathy , cardiac fibrosis , cardiac output , receptor , hemodynamics
We tested whether losartan would improve ventricular function and reverse both cardiac and skeletal Ca 2+ handling abnormalities in mice lacking α 2A ‐ and α 2C ‐ adrenoceptors (KO), which display sympathetic hyperactivity‐induced HF. Losartan (10 mg.kg −1 .day −1 ) was administered by tap water during 8‐wk (from 5 to 7 months of age, when cardiomyopathy is in an advanced‐stage). KO mice displayed reduced fractional shortening, cardiac dilation, exercise intolerance, lung edema, increased cardiomyocyte width and increased ventricular collagen content. Cardiac dysfunction was paralleled by changes in both cardiac and skeletal Ca 2+ handling abnormalities, such as decreased cardiac SERCA2 while increased NCX, and decreased soleus SERCA2 and NCX expression levels compared with age‐matched WT. Losartan treatment in KO mice restored fractional shortening, cardiac chamber size and exercise tolerance. As expected, losartan reduced cardiac myocyte width and ventricular fibrosis in KO mice. Interestingly, losartan treatment in KO mice increased cardiac SERCA2 expression towards WT levels, which was paralleled by decreased phospho‐Ser 16 ‐PLN and phospho‐Thr 17 ‐PLN. Likewise, losartan treatment in KO increased soleus SERCA2 expression to WT levels, while it had no impact on cardiac and skeletal NCX expression. Altogether, we provide evidence that losartan induces ventricular reverse remodeling and improves cardiac function in KO mice. This response is associated to an improved net balance of cardiac and skeletal Ca 2+ handling protein expression. FAPESP 04/04042‐0