title: Aldosterone blockade reduces mortality without changing cardiac remodeling in spontaneously hypertensive rats.
abstract: BACKGROUND
  The role of aldosterone blockers during transition from long-term compensated hypertrophy to dilated failure is not completely understood. In this study we evaluated the effects of early administration of spironolactone on cardiac remodeling, myocardial function, and mortality in spontaneously hypertensive rats (SHR).
  
  
  METHODS
  Sixteen-month-old SHR received no treatment (SHR-C, n=72) or spironolactone (SHR-SPR, 20 mg/kg/day, n=34) for six months. Echocardiogram was performed before and after treatment. Myocardial function was analyzed in left ventricular (LV) papillary muscle preparations. Myocardial collagen and hydroxyproline concentration were evaluated by morphometry and spectrophotometry, respectively. LV gene expression was assessed by real time RT-PCR.
  
  
  METHODS
  Student's t test; Log rank test (Kaplan Meyer).
  
  
  RESULTS
  SHR-C and SHR-SPR presented mortality rates of 71 and 38%, respectively (p=0.004). Systolic arterial pressure did not differ between groups (SHR-C 199±43; SHR-SPR 200±35 mmHg). Initial and final echocardiograms did not show significant differences in cardiac structures or LV function between groups. Myocardial function was similar between groups at basal and after inotropic stimulation. Collagen fractional area, hydroxyproline concentration, gene expression for α- and β-myosin heavy chain, atrial natriuretic peptide, and Serca2a were not different between groups.
  
  
  CONCLUSIONS
  Early spironolactone administration reduces mortality without changing cardiac remodeling in spontaneous hypertensive rats.
authors.affiliation: Botucatu Medical School, UNESP, Botucatu, Brazil.
authors.forename: Marcelo D M
authors.initials: MD
authors.lastname: Cezar
authors.forename: Ricardo L
authors.initials: RL
authors.lastname: Damatto
authors.forename: Paula F
authors.initials: PF
authors.lastname: Martinez
authors.forename: Aline R R
authors.initials: AR
authors.lastname: Lima
authors.forename: Dijon H S
authors.initials: DH
authors.lastname: Campos
authors.forename: Camila M
authors.initials: CM
authors.lastname: Rosa
authors.forename: Daniele M
authors.initials: DM
authors.lastname: Guizoni
authors.forename: Camila
authors.initials: C
authors.lastname: Bonomo
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Cicogna
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Gimenes
authors.forename: Luana U
authors.initials: LU
authors.lastname: Pagan
authors.forename: Marina P
authors.initials: MP
authors.lastname: Okoshi
authors.forename: Katashi
authors.initials: K
authors.lastname: Okoshi
mesh_terms: D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D004562:Electrocardiography; D005786:Gene Expression Regulation / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000401:mortality* / Q000503:physiopathology; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D010210:Papillary Muscles / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D011918:Rats, Inbred SHR; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics; D013148:Spironolactone / Q000008:administration & dosage / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases