Effect of chronic treatment with Sildenafil on cardiac hypertrophy

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

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Previously, we showed that myocardial Na+/H+ exchanger (NHE1)hyperactivity is responsible of cardiac hypertrophy (CH) developmentin spontaneously hypertensive rats (SHR), also that the increasedin protein Kinase G (PKG) activity after phosphodiesterase-5A (PDE5A) inhibition (Sildenafil, ?SIL?) inhibits NHE1. Currentstudy was aimed to evaluate the ability of chronic SIL treatment toreverse hypertrophy. As an initial approach, H9C2 cells were treatedduring 48hs with several doses of Angiotensin II (AngII) to inducegrowth (evaluated by measuring cell area in percent of control). Adose of 10nM AngII was then selected. A significant increase in cellarea 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 duringthe last 24hs of AngII treatment promoted a significant dose-dependentdecrease in cell area: 126±5% (5μM), 114±4% (10μM). Toevaluate in vivo the effect of SIL on CH, 4-months old SHR ratswere chronically treated (3 months) with SIL (100mg/kg/day) orallythrough drinking water (SHR+SIL) and compared to age-matcheduntreated controls (SHR). SIL reduced CH (left ventricular weightto body weight ratio: 2.69±0.04 vs. 2.52±0.05, p