Identification of amino-terminal pro-C-type natriuretic peptide in human plasma

We report the first identification of a circulating peptide from the amino- terminal end of proCNP. A specific radioimmunoassay was established based o n antisera to the synthetic peptide proCNP(1-15). Extracts of plasma, drawn from patients with congestive heart failure or from sheep with experimenta l heart failure, were subjected to size exclusion and reverse-phase high-pr essure liquid chromatography (HPLC) coupled to radioimmunoassay (RIA). Thes e studies revealed the presence of an immunoreactive peptide with a molecul ar weight (M-r approximately 5 kDa) similar to that expected for NT-proCNP( 1-50), a potential fragment released during processing of pro(CNP). The sam e material was isolated from extracts of homogenized ovine pituitary, a tis sue known to be a relatively enriched source of CNP. Plasma NT-proCNP level s in 22 patients with congestive heart failure (9.7 +/-0.5 pmol/L, mean +/- SEM, range 5.4-13.7 pmol/L) were raised (P=0.003) compared to those in 16 healthy volunteers (7.4 +/-0.3 pmol/L, range 5.7-10.7 pmol/L) and were high er than levels reported for CNP in similar subjects. This first identificat ion of circulating NT-proCNP opens the possibility of studying the factors regulating CNP production and metabolism in vivo. (C) 2001 Academic Press.