PERSONAL DE APOYO
PINILLA Oscar Andres
congresos y reuniones científicas
Título:
Inhibition of phosphodiesterase-5A by sildenafil attenuates dysfunction after myocardial infarction and decreases Na+/H+ exchanger expression
Autor/es:
PEREZ NG; ENNIS IL; GARCIARENA CD; PINILLA OA; ESCUDERO EM; CINGOLANI OH; CHIAPPE DE CINGOLANI G; CINGOLANI HE; YANG X-P
Lugar:
Dallas
Reunión:
Congreso; Scientific Sessions of The American Heart Association. Dallas, Texas, USA, Noviembre 2005; 2005
Institución organizadora:
American Heart Association
Resumen:
Introduction: Inhibition of phosphodiesterase-5A (PDE5A) by sildenafil (S) improves left ventricular remodeling in pressure-overloaded hearts. Accordingly, we hypothesized that by virtue of its effects it would improve remodeling after myocardial infarction (MI). Methods and Results: MI was induced by ligation of the left anterior descending coronary artery in 3?4 months-old-male Wistar rats. Immediately after coronary ligation, rats were randomized to placebo or S (100 mg/Kg/day), orally administered in drinking water for 6 weeks. After completion of treatment and before sacrifying the animals, fractional shortening (FS), determined by echocardiography, and hemodynamic contractility parameters were determined. Myocytes cross sectional area (CSA) as well as left ventricle brain natriuretic peptide (BNP) and Na/H exchanger (NHE-1) expression were also measured. PDE5A inhibition was confirmed by measuring left ventricle protein kinase G (PKG) activity after treatment (in fmol PO4/min/g protein: sham 5.640.23 n4, MI 4.850.95 n5, MIS 6.740.42 n5, P0.05 MIS vs sham and MI, ANOVA). S treatment significantly increased FS and dP/dt/IP (where IP is LV pressure at which dP/dt occurs) and decreased BNP and NHE expression, without significant changes in left ventricular mass (LVM) or myocytes CSA (Table). Conclusions: These data suggest that chronic inhibition of PDE5A for 6 weeks after myocardial infarction in the rat increases PKG activity and attenuates dysfunction after MI without affecting ventricular remodeling. Since it is widely accepted that inhibition of NHE-1 attenuates post ischemic functional disarrangements and it has been suggested that PKG activation blunts the enhanced 1204 Circulation Research Vol 97, No 11 November 25, 2005 Downloaded from http://circres.ahajournals.org/ by guest on October 17, 2014
