ATRIAL-NATRIURETIC-FACTOR IN OVINE PREGNANCY - PLASMA-LEVELS, MOLECULAR-FORMS AND BIOLOGICAL-ACTIVITY

Pregnancy is associated with hypervolemia and elevated plasma ANF, but the time course over which ANF increases and the mechanisms that cont rol plasma ANF levels are unclear. Plasma ANF was measured in 12 nonpr egnant and 16 pregnant sheep at various gestational ages. ANF was elev ated at 30-35 days of pregnancy (15.7 +/- 1.4 vs. 22.9 +/- 3.4 fmol/ml , P = 0.04), but did not increase further with the advance of gestatio n. Tissue content of ANF was unchanged in the right atrium, left atriu m, renal cortex, renal medulla, adrenals and lungs, but ovarian ANF co ntent was increased during pregnancy (9.2 +/- 2.2 vs. 67.2 +/- 23.2 fm ol/mg protein, P = 0.003). However, the ovarian tissue ANF concentrati on was less than 0.2% of that in the atria during pregnancy. HPLC of p lasma from both nonpregnant and pregnant ewes revealed the presence of a single peak that elutes in parallel with synthetic human ANF. HPLC of atrial and lung tissue homogenates revealed multiple peaks that may represent different molecular forms of ANF. The biological activity o f ANF in the plasma of pregnant ewes was reduced to 23% of nonpregnant levels. ANF in lung tissue was also biologically active, but that act ivity was reduced to 13% of nonpregnant levels. These data suggest tha t elevated plasma ANF in pregnancy is not secondary to increased atria l, renal, adrenal, ovarian or pulmonary contribution. Since we have pr eviously shown that the metabolic clearance of ANF is not decreased, o ther extra-atrial sites may contribute to the increased plasma ANF dur ing pregnancy. In addition, ovine pregnancy is associated with similar molecular forms of ANF but these exhibit reduced biological activity and may, therefore, alter volume regulation during pregnancy.