Mouse models imply that the phosphodiesterase 5 inhibitor sildenafil (SIL), via increasing cGMP, protects against angiotensin II (Ang II) stimulated cardiac remodeling. It is unclear which cell types are involved in these effects, because Ang II may exert its adverse effects by modulating multiple reno-vascular and cardiac functions via Ang II type 1 receptors (AT1R). In this study, to test the hypothesis that SIL/cGMP opposes cardiac stress provoked by amplified Ang II/AT1R directly in cardiomyocytes (CMs), transgenic mice with CM-specific overexpression of the AT1R under the control of the α-myosin-heavy chain promoter (αMHC-AT1Rtg/+) were studied. The extent of cardiac growth was assessed in absence or presence of SIL. Prolonged SIL treatment did not limit the progressive CM growth, fibrosis or decline in cardiac functions in the αMHC-AT1Rtg/+ model suggesting that SIL does not interfere with the pathogenic actions of amplified AT1R signaling in CMs.
See article at J Pharmacol Exp Ther 2015, 354:406–416.
- Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics