Metabolic clearance studies of atrial natriuretic peptide in normal pregnancy

Abstract

I read with interest the article of Irons et al. (Irons DW, Baylis PH, Davison JM. The metabolic clearance of atrial natriuretic peptide during human pregnancy. Am J Obstet Gynecol 1996; 175: 449-54). Our experience in a larger, yet cross-sectional, sample of 25 nonpregnant and 30 pregnant healthy women in the third trimester was similar (unpublished observation). Plasma atrial natriuretic peptide (ANP) levels were significantly higher in the pregnant group and with a significant positive correlation with gestational age (+0.39, p < 0.05). Increased renal clearance of ANP during pregnancy is usually blamed for the similar plasma hormone levels noted in pregnant and nonpregnant women in some previous studies, yet such clearance has never been measured.1Castro LC Hobel CJ Gornbein J Plasma levels of atrial natriuretic peptide in normal and hypertensive pregnancies; a metaanalysis.Am J Obstet Gynecol. 1994; 171: 1642-1651Abstract Full Text PDF PubMed Google Scholar The work of Irons et al., however, indicates that in spite of increased clearance in pregnancy atrial secretion of ANP probably increases to a greater extent, producing a net increase in plasma hormone levels. The hypervolemia of pregnancy is thus sensed by atrial stretch receptors. In contrast to most previous studies,1Castro LC Hobel CJ Gornbein J Plasma levels of atrial natriuretic peptide in normal and hypertensive pregnancies; a metaanalysis.Am J Obstet Gynecol. 1994; 171: 1642-1651Abstract Full Text PDF PubMed Google Scholar we did not observe a significant difference between plasma ANP levels in normotensive pregnant women and in 30 gestational age–matched patients with preeclampsia. Because there is no evidence in the literature that intraatrial pressure is increased in preeclampsia,2Steegers EA Atrial natriuretic peptide during human pregnancy and puerperium.Fetal Med Rev. 1991; 3: 185-196Crossref Scopus (5) Google Scholar our hypothesis was that lower plasma ANP levels would be expected compared with normal pregnancy because of decreased intravascular volume. Preeclamptic patients in our series had significantly raised serum creatinine levels, possibly caused by decreased glomerular filtration rate. Clearance of ANP in pregnancy is primarily by the kidneys and is affected by changes in glomerular filtration rate (Irons et al.). A likely explanation therefore could be that plasma ANP levels were apparently raised in our preeclamptic group as a result of reduced renal clearance. Serial measurement of metabolic clearance rate of ANP in preeclampsia, the subsequent research endeavor of Irons et al., might clarify whether circulating ANP levels are changed and whether this is caused by changes in hormone secretion or metabolic clearance. There was a significant negative correlation between serum sodium and plasma ANP levels in all pregnant subjects of our study (−0.51, p < 0.05), suggesting a natriuretic action of ANP in human pregnancy. Irons et al. showed that natriuresis not only occurs after administration of ANP to normotensive pregnant women but, more important, this effect is dose related. Given the safe infusion regimen of the authors and the additional vasodilating properties of ANP, it seems reasonable and therapeutically relevant to repeat such a procedure in preeclamptic patients.