FETAL RENAL RESPONSE TO ATRIAL-NATRIURETIC-FACTOR DECREASES WITH MATURATION

The presence of atrial natriuretic factor (ANF) in fetal tissues and plasma early in gestation suggests that ANF may have a physiological role in cardiocirculatory homeostasis in utero. However, reported responsiveness of the fetal kidney to ANF varies markedly. To characterize the ontogeny of fetal renal responsiveness to ANF, chronically catheterized ovine fetuses at 114 +/- 1 days (n = 6) and 131 +/- 1 days (n = 6) received successive (30 min each) intravenous infusions of ANF at rates of 5, 25, and 100 ng. min-1.kg-1. Mean (+/- SE) fetal plasma ANF levels increased from 328 +/- 54 to 1,866 +/- 482 and 521 +/- 135 to 1,579 +/- 295 pg/ml in the younger and more mature fetuses, respectively. Mean urine volume (0.17 +/- 0.03 to 0.37 +/- 0.09 ml.min-1.kg-1) and GFR (0.9 +/- 0.2 to 1.8 +/- 0.4 ml.min-1.kg-1) increased in the early gestation fetuses but did not change in the older fetuses. Mean urine sodium excretion and osmolar clearance increased by 352 and 155% in the early gestation fetal lambs and 118 and 50% in the older animals. The fetal plasma ANF clearance rates (PC(ANF) were lower in the early vs. the late gestation fetuses (68 +/- 15 vs. 116 +/- 28 ml.min-1.kg-1, respectively). These results demonstrate a decrease in fetal renal responsiveness to ANF with advancing fetal age. Multiple factors appear to contribute, including changes in PC(ANF) and maturational changes in glomerular filtration rate, renal tubular function and ANF receptor metabolism.