Metabolism of atrial and brain natriuretic peptides in the fetoplacental circulation of fetuses with congenital heart diseases.

INTRODUCTION

Natriuretic peptides (NPs) play a pivotal role in maintaining fetal circulation; however, little is known about their metabolism. The aim of the present study was to elucidate the metabolism of plasma NPs in the fetoplacental circulation.

METHODS

Plasma NP concentrations in maternal vein and umbilical artery (UA) and vein (UV) samples from fetuses with congenital heart defect (n = 86) or arrhythmia (n = 31) and controls (n = 127) were analyzed.

RESULTS

Levels of plasma atrial NP (ANP) and brain NP (BNP) showed good correlation between UV versus UA samples (p < 0.01). In all three fetus groups, the regression coefficients between UV and UA plasma ANP levels were close to 0.5, while those between UV and UA plasma BNP levels were close to 1. The molecular forms of immunoreactive ANP in UA plasma showed a single peak corresponding to mature ANP, while those of immunoreactive BNP in UA plasma showed two major peaks and several minor peaks corresponding to mature BNP-32 and its partially digested peptides, as well as glycosylated and non-glycosylated BNP precursors (proBNP). No correlation was found between fetuses and mothers in terms of either plasma ANP or BNP levels.

CONCLUSIONS

The mother and fetus independently secrete and metabolize both ANP and BNP. Fetal plasma ANP consists exclusively of the mature form, and the placenta and umbilical vessels are possible major sites of ANP metabolism. In contrast, fetal plasma BNP consists predominantly of the precursor forms, which may contribute to protecting BNP from metabolism in the fetoplacental circulation.