title: Effects of spironolactone in spontaneously hypertensive adult rats subjected to high salt intake.
abstract: OBJECTIVE
  To evaluate the effect of spironolactone on ventricular stiffness in spontaneously hypertensive adult rats subjected to high salt intake.
  
  
  BACKGROUND
  High salt intake leads to cardiac hypertrophy, collagen accumulation and diastolic dysfunction. These effects are partially mediated by cardiac activation of the renin-angiotensin-aldosterone system.
  
  
  METHODS
  Male spontaneously hypertensive rats (SHRs, 32 weeks) received drinking water (SHR), a 1% NaCl solution (SHR-Salt), or a 1% NaCl solution with a daily subcutaneous injection of spironolactone (80 mg.kg⁻¹) (SHRSalt- S). Age-matched normotensive Wistar rats were used as a control. Eight weeks later, the animals were anesthetized and catheterized to evaluate left ventricular and arterial blood pressure. After cardiac arrest, a double-lumen catheter was inserted into the left ventricle through the aorta to obtain in situ left ventricular pressure-volume curves.
  
  
  RESULTS
  The blood pressures of all the SHR groups were similar to each other but were different from the normotensive controls (Wistar = 109 ± 2; SHR = 118 ± 2; SHR-Salt = 117 ± 2; SHR-Salt-S = 116 ± 2 mmHg; P < 0.05). The cardiac hypertrophy observed in the SHR was enhanced by salt overload and abated by spironolactone (Wistar = 2.90 ± 0.06; SHR = 3.44 ± 0.07; SHR-Salt = 3.68 ± 0.07; SHR-Salt-S = 3.46 ± 0.05 mg/g; P < 0.05). Myocardial relaxation, as evaluated by left ventricular dP/dt, was impaired by salt overload and improved by spironolactone (Wistar = -3698 ± 92; SHR = -3729 ± 125; SHR-Salt = -3342 ± 80; SHR-Salt-S = -3647 ± 104 mmHg/s; P < 0.05). Ventricular stiffness was not altered by salt overload, but spironolactone treatment reduced the ventricular stiffness to levels observed in the normotensive controls (Wistar = 1.40 ± 0.04; SHR = 1.60 ± 0.05; SHR-Salt = 1.67 ± 0.12; SHR-Salt- S = 1.45 ± 0.03 mmHg/ml; P < 0.05).
  
  
  CONCLUSIONS
  Spironolactone reduces left ventricular hypertrophy secondary to high salt intake and ventricular stiffness in adult SHRs.
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil. marcelobaldo@ymail.com
authors.forename: Marcelo Perim
authors.initials: MP
authors.lastname: Baldo
authors.forename: Divanei
authors.initials: D
authors.lastname: Zaniqueli
authors.forename: Ludimila
authors.initials: L
authors.lastname: Forechi
authors.forename: Rebeca Caldeira
authors.initials: RC
authors.lastname: Machado
authors.forename: Sérgio Lamêgo
authors.initials: SL
authors.lastname: Rodrigues
authors.forename: José Geraldo
authors.initials: JG
authors.lastname: Mill
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy*; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000209:etiology; D016014:Linear Models; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage* / Q000009:adverse effects*; D013148:Spironolactone / Q000627:therapeutic use*; D013997:Time Factors; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D017673:Sodium Chloride, Dietary; D013148:Spironolactone