There are several peptides, such as the natriuretic peptides (NPs) that help to ameliorate all the harmful effects of SNS and Renin Angiotensin and Sympathetic Nervous System (RAAS) by attenuating vasoconstriction, sodium retention, and retarding cardiac and vascular remodeling. NPs are coupled to, and activate, guanyl cyclase A, which increases the intracellular concentrations of cyclic guanosine monophosphate, helping and leading to vasorelaxation, natriuresis, and diuresis. B-type natriuretic peptide (BNP) also inhibit renin secretion and aldosterone production and attenuate cardiac and vascular remodeling, apoptosis, ventricular hypertrophy, and fibrosis.

The failing heart becomes an exocrine gland increasing the release of peptid natriuretics

Normally, these compensatory actions are not sufficient to prevent or stop HF development because NPs are readily destroyed by an enzyme, neprilysin (currently the new drug Entresto, has double effect: inhibition of RAAS and inhibition of neprilysin).