Natriuretic peptides – alternative pathways for the activation of intracellular signaling axis – cyclic guanylyl-monophosphate-protein kinase G at the background of preserved ejection fraction during chronic heart failure

Abstract

At the background of preserved ejection fraction clinical and
hemodynamic impairment developed in the patients with heart failure (HFpEF) significantly
is associated with progression of diastolic dysfunction of left ventricle (LV). A key role in the
maintaining normal diastolic heart function is assigned to a high level of intracellular
signaling axis – cyclic guanylyl-monophosphate-protein kinase G (cGMP-PK-G) activation,
which significantly reduces during HFpEF.
Besides nitrogen oxide (NO), natriuretic peptides (NPs) also have the ability to activate the
intracellular signaling axis. However, by neutral endopeptidase – neprilysin, NPs are
rapidly degraded and fail to develop clinically significant effects. The neprilysin inhibitors
appear to be one of the mechanisms for NPs level increasing. The opportunities for the
usage of Sacubitril-Valsartan during HFpEF have been analyzed.