Sildenafil treatment decreases cardiac hypertrophy and stiffness in young spontaneously hypertensive rats (SHR)

ESCUDERO DS; DI CIANNI L; PÉREZ NG; DÍAZ RG

La Plata

Congreso; Annual Meeting of the International Society for Heart Research (ISHR) Latin American Section; 2022

International Society for Heart Research (ISHR) Latin American Section

Sildenafil (SIL), a highly specific phosphodiesterase 5A (PDE5A) inhibitor used as vasoactive drug in the treatment of erectile dysfunction, possesses cardioprotective properties. Cardiac Na+/H+ exchanger (NHE1) plays an essential role to maintain proper cell function by regulating intracellular pH, but its hyperactivity has been linked to the development of several cardiac pathologies. In line, previous own experiments performed in adult (8 month-old) SHR, a well-known model of hypertensive cardiac hypertrophy (CH) where NHE1 hyperactivity is a hallmark, demonstrated that chronic SIL treatment reduces NHE1 activity, leading to reduction of CH and fibrosis. The present work was aimed to evaluate whether similar effects can be obtained in young SHR. 4-month-old animals were treated with 100mg/Kg/day of SIL through drinking water during 3 months (n=4). Non-treated age-matched SHR were used as control (C, n=4). SIL treatment did not modified blood pressure (weekly monitored), but significantly reduced CH (Left Ventricular Weight/Body Weight) from 2.69±0.04 (C) to 2.52±0.05 mg/g (p=0.03), and myocardial stiffness from 1.17±0.21 (C) to 0.41±0.19 g/mm2, p=0.045). In conclusion, chronic SIL treatment reduced CH an improved diastolic function also in young animals. These effects were not related to vascular mechanisms, but may preliminary be assigned to the inhibitory effect of SIL on NHE1 in the myocardium.