title: Effects of early aldosterone antagonism on cardiac remodeling in rats with aortic stenosis-induced pressure overload.
abstract: Aldosterone plays a pivotal role in the pathophysiology of systolic heart failure. However, whether early aldosterone antagonism improves cardiac remodeling during persistent pressure overload is unsettled. We evaluated the effects of aldosterone antagonist spironolactone on cardiac remodeling in rats with ascending aortic stenosis (AS).
  
  
  METHODS
  Three days after inducing AS, weaning rats were randomized to receive spironolactone (AS-SPR, 20mg/kg/day) or no drug (AS) for 18weeks, and compared with sham-operated rats. Myocardial function was studied in isolated left ventricular (LV) papillary muscles.
  
  
  METHODS
  ANOVA or Kruskal-Wallis tests.
  
  
  RESULTS
  Echocardiogram showed that LV diastolic (Sham 8.73±0.57; AS 8.30±1.10; AS-SPR 9.19±1.15mm) and systolic (Sham 4.57±0.67; AS 3.61±1.49; AS-SPR 4.62±1.48mm) diameters, left atrial diameter (Sham 5.80±0.44; AS 7.15±1.22; AS-SPR 8.02±1.17mm), and LV mass were higher in AS-SPR than AS. Posterior wall shortening velocity (Sham 38.5±3.8; AS 35.6±5.6; AS-SPR 31.1±3.8mm/s) was lower in AS-SPR than Sham and AS; E/A ratio was higher in AS-SPR than Sham. Developed tension was lower in AS and AS-SPR than Sham. Time to peak tension was higher in AS-SPR than Sham and AS after post-rest contraction. Right ventricle weight was higher in AS-SPR than AS, suggesting more severe heart failure in AS-SPR than AS. Interstitial collagen fractional area and myocardial hydroxyproline concentration were higher in AS than Sham. Metalloproteinase-2 and -9 activity, evaluated by zymography, did not differ between groups.
  
  
  CONCLUSIONS
  Early spironolactone administration causes further hypertrophy in cardiac chambers, and left ventricular dilation and dysfunction in rats with AS-induced chronic pressure overload.
authors: Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University, UNESP, Brazil. Electronic address: mpoliti@fmb.unesp.br.
authors: M P
authors: MP
authors: Okoshi
authors: Itapeva Social and Agrarian Sciences College, FAIT, Itapeva, SP, Brazil.
authors: M D M
authors: MDM
authors: Cezar
authors: Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University, UNESP, Brazil.
authors: R M
authors: RM
authors: Iyomasa
authors: Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University, UNESP, Brazil.
authors: M B
authors: MB
authors: Silva
authors: Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University, UNESP, Brazil.
authors: L C O
authors: LCO
authors: Costa
authors: Federal University of Mato Grosso do Sul, Campo Grande, Brazil.
authors: P F
authors: PF
authors: Martinez
authors: Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University, UNESP, Brazil.
authors: D H S
authors: DHS
authors: Campos
authors: Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University, UNESP, Brazil; Itapeva Social and Agrarian Sciences College, FAIT, Itapeva, SP, Brazil.
authors: R L
authors: RL
authors: Damatto
authors: Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University, UNESP, Brazil.
authors: M F
authors: MF
authors: Minicucci
authors: Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University, UNESP, Brazil.
authors: A C
authors: AC
authors: Cicogna
authors: Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University, UNESP, Brazil.
authors: K
authors: K
authors: Okoshi
mesh_terms: D000450:Aldosterone / Q000502:physiology*; D000818:Animals; D001024:Aortic Valve Stenosis / Q000139:chemically induced / Q000503:physiopathology*; D006332:Cardiomegaly / Q000139:chemically induced / Q000503:physiopathology*; D004562:Electrocardiography / Q000187:drug effects / Q000639:trends; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000633:toxicity*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013148:Spironolactone / Q000633:toxicity; D016896:Treatment Outcome; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology*
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000450:Aldosterone
keywords: Cardiac hypertrophy; Myocardial fibrosis; Papillary muscle; Spironolactone; Ventricular function