Mutation of three amino acids in the disulfide-ring of a CNP based chimeric natriuretic peptide alters its vascular properties

Abstract

Clinical background C-type natriuretic peptide (CNP) is a 22-amino-acid peptide produced mainly in the endothelium with potent cardiac unloading and blood pressure lowering actions, but minimal renal actions. Based on our previous knowledge, we recently fused a 6 aa sequence from BNP to the C-terminus and a 5 aa sequence from ANP to the N-terminus of CNP. This novel hybrid peptide, CBA-NP, has cardiac unloading actions and mild hypotensive effects similar to CNP. Importantly however, the N and C terminus alterations resulted in potent renal excretory actions. Here we test the hypothesis that the 3 aa GSM15–17 in the disulfidering mediate the vascular and hypotensive actions of CBANP. We therefore mutated GSM 15–17 to REA15–17, which we named ABC-NP and compared its in vivo and in vitro actions to CBA-NP.