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The aim of the present study was to evaluate the effect of low-dose spironolactone initiated during the early stages of hypertension development and to assess the effects of chronic pressure overload on ventricular remodeling in rats. Male spontaneously hypertensive rats (SHRs) (4 weeks) were randomized to receive daily spironolactone (20 mg/kg) or vehicle (mineral oil) from 4 weeks to 8 months of age. Systolic blood pressure was measured non-invasively by tail-cuff pletysmography at baseline, 4 and 8 months. Hemodynamic assessment was performed at the end of treatment by arterial and ventricular catheterization. An in situ left ventricular pressure-volume curve was created to evaluate dilatation and wall stiffness. Systolic blood pressure at 1 month of age was higher in SHRs than in the Wistar group; it increased throughout the follow-up period and remained elevated with treatment (Wistar: 136 ± 2, SHR: 197 ± 6.8, SHR-Spiro: 207 ± 7.1 mmHg; p < 0.05). Spironolactone reduced cardiac hypertrophy (Wistar: 1.25 ± 0.03 SHR: 1.00 ± 0.03, SHR-Spiro: 0.86 ± 0.02 g; p < 0.05) and left ventricular mass normalized to body weight (Wistar: 2.51 ± 0.06, SHR: 2.70 ± 0.08, 2.53 ± 0.07 mg/g; p < 0.05). Moreover, the left ventricular wall stiffness that was higher in SHRs was partially reduced by spironolactone treatment (Wistar: 0.370 ± 0.032; SHR: 0.825 ± 0.058; SHR-Spiro: 0.650 ± 0.023 mmHg/ml; p < 0.05). Our results show that long-term spironolactone treatment initiated at the early stage of hypertension development reduces left ventricular hypertrophy and wall stiffness in SHRs.

OBJECTIVE:To evaluate the effect of spironolactone on ventricular stiffness in spontaneously hypertensive adult rats subjected to high salt intake.INTRODUCTION: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) (SHR-Salt-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).CONCLUSION:Spironolactone reduces left ventricular hypertrophy secondary to high salt intake and ventricular stiffness in adult SHRs.

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