A novel aquaretic and GFR enhancing peptide without vascular vasodilatory actions in experimental CHF

Abstract

Background: BNP is a cardiac peptide with vasodilatory, natriuretic and diuretic properties. Recent studies have suggested that its vasodilatory hypotensive properties may limit the renal actions of BNP, especially in patients with borderline low blood pressure. We have recently identified an alternatively spliced transcript for BNP (ASBNP) that includes a unique and distinct longer carboxyl-terminus consisting of 34 amino acids. Based upon preliminary studies, we generated a truncated form (ASBNP2.1) that contains the first 16 amino acids of the C-terminal of ASBNP. Method: We determined the cardiorenal and humoral actions of intravenous infusion of ASBNP2.1 at 2 pmol/kgmin, 10 pmol/kgmin and 100pmol/kgmin in 10 dogs with rapid ventricular pacing induced overt CHF (240 bpm for 10 days) (*p< 0.05). Results: IV infusion of ASBNP 2.1 increased aquaresis (from 0.19± 0.04 to 0.32± 0.07, 0.46± 0.11 and 0.39± 0.09ml/min*) without a significant change in urinary sodium excretion. Importantly, ASBNP 2.1 enhanced glomerular filtration rate (GFR), from 31± 4 to 47± 8, Titration of medications byHF nurses increases optimisation doses of key therapeutic agents