The novel dual GC-A and GC-B designer natriuretic peptide, cenderitide (CD-NP), enhances the renal actions of furosemide in a model of severe heart failure

Abstract

Background Patients with congestive heart failure (HF) have symptomatic improvement with diuretic therapy, although with time diuretic resistance and renal dysfunction can occur. Cenderitide (also known as CD-NP), now in clinical trials in patients with HF, is a Mayo designed chimeric natriuretic peptide which, unlike the native natriuretic peptides (NPs) ANP, BNP and CNP, binds both to guanylyl cyclase (GC)-B and GC-A with greater affinity for GC-B. Cenderitide thus was designed to mediate more venodilation than arterial dilation via GC-B and so result in less hypotension than BNP or ANP, but unlike CNP also possess natriuretic and diuretic properties via GC-A activation. We tested the hypothesis that combining cenderitide with furosemide will produce increased diuresis and natriuresis compared to furosemide alone without causing excessive hypotension or renal dysfunction in experimental HF.