Effect of chronic treatment with sildenafil on cardiac hypertrophy

DÍAZ RG; DI CIANNI L; CIANCIO MC; PORTIANSKY EL; ESCUDERO DS; PINILLA OA; PÉREZ NG

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Sociedades Argentinas de Biociencias (en conjunto)

Previously, we showed that myocardial Na+/H+ exchanger (NHE1) hyperactivity is responsible of cardiac hypertrophy (CH) development in spontaneously hypertensive rats (SHR), also that the increased in protein Kinase G (PKG) activity after phosphodiesterase-5A (PDE5A) inhibition (Sildenafil, ?SIL?) inhibits NHE1. Current study was aimed to evaluate the ability of chronic SIL treatment to reverse hypertrophy. As an initial approach, H9C2 cells were treated during 48hs with several doses of Angiotensin II (AngII) to induce growth (evaluated by measuring cell area in percent of control). A dose of 10nM AngII was then selected. A significant increase in cell area was detected after 24hs of AngII: 129±6 vs.100±5% (control), n=4, effect that was larger after 48hs: 154±8%. Addition of SIL during the last 24hs of AngII treatment promoted a significant dose-dependent decrease in cell area: 126±5% (5µM), 114±4% (10µM). To evaluate in vivo the effect of SIL on CH, 4-months old SHR rats were chronically treated (3 months) with SIL (100mg/kg/day) orally through drinking water (SHR+SIL) and compared to age-matched untreated controls (SHR). SIL reduced CH (left ventricular weight to body weight ratio: 2.69±0.04 vs. 2.52±0.05, p