Effects of spironolactone in spontaneously hypertensive adult rats subjected to high salt intake.

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) (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).

Conclusion: Spironolactone reduces left ventricular hypertrophy secondary to high salt intake and ventricular stiffness in adult SHRs.