Sildenafil stops progressive chamber, cellular, and molecular remodeling and improves calcium handling and function in hearts with pre-existing advanced hypertrophy caused by pressure overload.

ABSTRACT:

Objective

This study sought to test the efficacy of phosphodiesterase type 5A (PDE5A) inhibition for treating advanced hypertrophy/remodeling caused by pressure overload, and to elucidate cellular and molecular mechanisms for this response.

Background

Sildenafil (SIL) inhibits cyclic guanosine monophosphate-specific PDE5A and can blunt the evolution of cardiac hypertrophy and dysfunction in mice subjected to pressure overload. Whether and how it ameliorates more established advanced disease and dysfunction is unknown.

Methods

Mice were subjected to transverse aortic constriction (TAC) for 3 weeks to establish hypertrophy/dilation, and subsequently treated with SIL (100 mg/kg/day) or placebo for 6 weeks of additional TAC.

Results

The SIL arrested further progres

SUBMITTER: Nagayama T 

PROVIDER: S-EPMC2978969 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature