Angiotensin receptor neprilysin inhibitors (ARNi) target multiple regulatory pathways in heart failure, modulating both vasodilator and vasoconstrictor peptides to produce composite clinical effects.
Understanding the multiple substrates of neprilysin provides insights into the expected on-target and off-target effects of ARNi therapy in heart failure.
The autonomic nervous system, the renin-angiotensin-aldosterone system, and the natriuretic peptide system represent critical regulatory pathways in heart failure and as such have been the major targets of pharmacological development. The introduction and approval of angiotensin receptor neprilysin inhibitors (ARNi) have broadened the available drug treatments of patients with chronic heart failure with reduced ejection fraction. Neprilysin catalyses the degradation of a number of vasodilator peptides, including the natriuretic peptides, bradykinin, substance P, and adrenomedullin, as well as vasoconstrictor peptides, including endothelin-1 and angiotensin I and II. We review the multiple, potentially competing, substrates for neprilysin inhibition, and the resultant composite clinical effects of ARNi therapy. A mechanistic understanding of this novel therapeutic class may provide important insights into the expected on-target and off-target effects when this agent is more widely prescribed.
D’Elia et al. (Tue,) conducted a review in chronic heart failure with reduced ejection fraction. angiotensin receptor neprilysin inhibitors (ARNi) was evaluated. Angiotensin receptor neprilysin inhibitors (ARNi) target multiple regulatory pathways in heart failure, modulating both vasodilator and vasoconstrictor peptides to produce composite clinical effects.
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