Sildenafil and B-type natriuretic peptide acutely phosphorylate titin and improve diastolic distensibility in vivo.

ABSTRACT:

Background

In vitro studies suggest that phosphorylation of titin reduces myocyte/myofiber stiffness. Titin can be phosphorylated by cGMP-activated protein kinase. Intracellular cGMP production is stimulated by B-type natriuretic peptide (BNP) and degraded by phosphodiesterases, including phosphodiesterase-5A. We hypothesized that a phosphodiesterase-5A inhibitor (sildenafil) alone or in combination with BNP would increase left ventricular diastolic distensibility by phosphorylating titin.

Methods and results

Eight elderly dogs with experimental hypertension and 4 young normal dogs underwent measurement of the end-diastolic pressure-volume relationship during caval occlusion at baseline, after sildenafil, and BNP infusion. To assess diastolic distensibility independently of

SUBMITTER: Bishu K 

PROVIDER: S-EPMC3412357 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature