Diurnal Plasma Concentrations of Natriuretic Propeptides in Healthy Young Males

To the Editor: Natriuretic peptides are a family of structurally related hormones encoded by genes for atrial natriuretic peptide (ANP),1 B-type natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). Although the bioactive peptides are related, their tissue and receptor specificities differ. Natriuretic peptide production can also be assessed by measuring the N-terminal fragments from their prohormones in plasma, because these fragments constitute stable markers in vitro and in vivo. The molecular heterogeneity of the propeptides has proved to be complex, and cardiac biosynthesis involves both endoproteolytic cleavage and posttranslational modification 1. The BNP precursor, for instance, is a glycosylated polypeptide and variably matures to the C-terminal, bioactive BNP hormone. The CNP products encoded by the NPPC 2 (natriuretic peptide C) gene have been difficult to measure accurately because their plasma concentrations are considerably lower than for the ANP and BNP peptides. Diurnal hormone production is a hallmark of many endocrine systems. In mouse models, expression of the genes encoding ANP and BNP has been shown to be regulated in a circadian manner by clock genes. We recently reported that BNP mRNA contents, but not ANP mRNA contents, are produced in a circadian manner in the ventricles of wild-type mice and that the production pattern reflects the local expression of the central clock genes Per1 [period homolog 1 …