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Neprilysin inhibition in heart failure: mechanisms and substrates beyond modulating natriuretic peptides
Author(s) -
D'Elia Emilia,
Iacovoni Attilio,
Vaduganathan Muthiah,
Lorini Ferdinando L.,
Perlini Stefano,
Senni Michele
Publication year - 2017
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1002/ejhf.799
Subject(s) - neprilysin , heart failure , bradykinin , medicine , natriuretic peptide , adrenomedullin , renin–angiotensin system , atrial natriuretic peptide , pharmacology , angiotensin ii , endocrinology , receptor , blood pressure , chemistry , enzyme , biochemistry
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.