The metabolic clearance of atrial natriuretic peptide during human pregnancy

OBJECTIVE: Our purpose was to determine whether human pregnancy alters the metabolic clearance and natriuretic effect of atrial natriuretic peptide. STUDY DESIGN: The metabolic clearance rate of atrial natriuretic peptide (ANP 99-126) was measured serially in nine normotensive primigravid women studied in early and late pregnancy and again 4 months post partum (nonpregnant). Metabolic clearance of atrial natriuretic peptide was determined by use of a two-tier constant infusion technique (6 and 12 ng/kg/min, respectively). Sodium excretion was determined from 30-minute urine collections taken before and during infusion of atrial natriuretic peptide at both 6 and 12 ng/kg/min. RESULTS: Basal plasma atrial natriuretic peptide levels increased with gestation: in early pregnancy 18.0 +/- 2.7 pg/ml, in late pregnancy 22.6 +/- 4.2 pg/ml, and post partum 19.5 +/- 3.6 pg/ml. Infusion of atrial natriuretic peptide at 6 and 12 ng/kg/min produced two distinct physiologic plasma levels of atrial natriuretic peptide. The metabolic clearance rates for nonpregnant women and those in early and late pregnancy at 6 and 12 ng/kg/min, respectively, were 3.4 +/- 0.4 and 2.9 +/- 0.4 L/min at plasma atrial natriuretic peptide levels of 86.2 +/- 13.2 and 179.8 +/- 42.5 pg/ml, respectively, 4.3 +/- 0.5 and 4.3 +/- 0.5 L/min at plasma atrial natriuretic peptide levels of 61.1 +/- 4.9 and 131 +/- 20.9 pg/ml (p < 0.01, nonpregnant vs early pregnancy), and 3.8 +/- 0.6 and 3.8 +/- 0.5 L/min at plasma atrial natriuretic peptide levels of 72 +/- 8.0 and 136 +/- 18.3 pg/ml (p < 0.05, nonpregnant vs late pregnancy), respectively. Infusion of atrial natriuretic peptide produced natriuresis in both pregnant and nonpregnant states; sodium excretion (basal to atrial natriuretic peptide infusion at 12 ng/kg/min) increased from 133 +/- 19 to 207 +/- 18 mu mol/min, 129 +/- 21 to 374 +/- 35 mu mol/min, and 128 +/- 20 to 221 +/- 33 mu mol/min in nonpregnant women and those in early and late pregnancy, respectively. CONCLUSIONS: The metabolic clearance of atrial natriuretic peptide increased by 16 weeks' gestation and remained elevated thereafter. There appears to be no attenuation of the natriuretic effect of infused atrial natriuretic peptide in normotensive human pregnancy.