AJP - Regulatory, Integrative and Comparative Physiology, Vol 267, Issue 5 1413-R1420, Copyright © 1994 by American Physiological Society
Metabolic clearance of atrial natriuretic factor in ovine pregnancy
S. Mukaddam-Daher, J. Gutkowska, B. S. Nuwayhid and E. W. Quillen Jr
Department of Obstetrics and Gynecology, McGill University, Montreal, Quebec, Canada.
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.
