Chronic inhibition of cGMP-specific phosphodiesterase 5 suppresses endoplasmic reticulum stress in heart failure.

ABSTRACT:

Background and purpose

Inhibition of the cGMP-specific phosphodiesterase 5 (PDE5) exerts profound beneficial effects on failing hearts. However, the mechanisms underlying the therapeutic effects of PDE5 inhibition on heart failure are unclear. The purpose of this study was to investigate whether PDE5 inhibition decreases endoplasmic reticulum (ER) stress, a key event in heart failure.

Experimental approach

Heart failure was induced by isoprenaline s.c. injection in Sprague-Dawley rats and transverse aortic constriction (TAC) in mice. PDE5 was inhibited with sildenafil. Heart function was detected by invasive pressure-volume analysis and echocardiography. ER stress markers were analysed by Western blotting. Apoptosis was measured by flow cytometric analysis.

Key results

SUBMITTER: Gong W 

PROVIDER: S-EPMC3838686 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature