Metabolic clearance of atrial natriuretic factor in ovine pregnancy

Plasma atrial natriuretic factor (ANF) is normally released into the circulation primarily by volume expansion and atrial distension, but we have shown that plasma ANF is elevated in pregnant sheep before volume expansion. Because alterations in the metabolic clearance of ANF could lead to elevated plasma ANF levels, the present study was designed to determine the pharmacokinetics of plasma ANF in pregnant sheep. Chronically instrumented nonpregnant and pregnant sheep received intravenous injections of monoiodinated human ANF (125I-hANF). Plasma decay curves of 125I-hANF followed a biexponential function in both groups. High-performance liquid chromatography (HPLC) revealed the accumulation of smaller degradation products by 2 min postinjection, and by 30 min no intact ANF was present. Because HPLC identification of ANF and its metabolites was shown to be more efficient than precipitation with 10% trichloroacetic acid (TCA) or extraction by Sep-Pak cartridges, ANF kinetic parameters were calculated from HPLC-corrected plasma decay curves. Injected ANF was rapidly distributed in an initial distribution volume (IDV) that was expanded in pregnant sheep. Metabolic clearance rate (MCR) was greater in pregnant sheep (2.8 +/- 0.3 vs. 6.8 +/- 1.2 l/min, P = 0.002), while plasma half-life (t1/2) was not altered (2.2 +/- 0.5 vs. 2.4 +/- 0.4 min). The data demonstrate that during pregnancy, the t1/2 of ANF is not altered but the MCR of ANF is enhanced. These findings imply that plasma ANF is increased by mechanisms other than reduced clearance in pregnant sheep.