Pathological cardiac hypertrophy alters intracellular targeting of phosphodiesterase type 5 from nitric oxide synthase-3 to natriuretic peptide signaling.

ABSTRACT:

Background

In the normal heart, phosphodiesterase type 5 (PDE5) hydrolyzes cGMP coupled to nitric oxide- (specifically from nitric oxide synthase 3) but not natriuretic peptide (NP)-stimulated guanylyl cyclase. PDE5 is upregulated in hypertrophied and failing hearts and is thought to contribute to their pathophysiology. Because nitric oxide signaling declines whereas NP-derived cGMP rises in such diseases, we hypothesized that PDE5 substrate selectivity is retargeted to blunt NP-derived signaling.

Methods and results

Mice with cardiac myocyte inducible PDE5 overexpression (P5(+)) were crossed to those lacking nitric oxide synthase 3 (N3(-)), and each model, the double cross, and controls were subjected to transaortic constriction. P5(+) mice developed worse dysfunction and h

SUBMITTER: Zhang M 

PROVIDER: S-EPMC3428375 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature