The tubuloglomerular feedback (TGF) mechanism is important in regulating single nephron GFR. The prenatal kidney has a high vascular tone and low GFR. After birth, vascular tone decreases, increasing GFR. It is not known, whether the TGF mechanism is active during fetal and neonatal life, maintaining vascular tone and GFR during this period. Therefore, we have investigated TGF characteristics before and after birth in ovine fetuses (133-140 days gestation) and lambs (12-17 days postnatal) during euvolemia and volume expansion. Fetuses were delivered through a cesarean incision with the umbilical cord intact. TGF activity was evaluated by measuring changes in proximal tubular stop-flow pressure (PSF) in response to various perfusion rates of the loop of Henle. Blood pressures in the fetuses and lambs were 54 ± 0.6 and 75 ± 1.2mmHg, respectively. In the fetus, free-flow pressure (PFF) was 6.5 ± 0.6 and PSF 29.3 ± 0.73mmHg. Maximal change in PSF (?PSF) was 4.9 ± 0.9 with the turning point (TP) at 16.3 ± 1.3nl/min. Volume expansion increased TP but did not affect PFF, PSF or ?PSF. In lambs, PFF was 9.0 ± 0.3 and PSF 34.0 ± 0.6mmHg. ?PSF was ~2-fold higher (10.6 ± 0.6mmHg) than in fetuses and the TP was 19.4 ± 1.1nl/min. Volume expansion decreased ?PSF to 4.3 ± 0.4 nl/min and increased the TP to 28.3 ± 1.7mmHg.

This is the first study showing that the TGF mechanism is active in the prenatal kidney. Furthermore, these data indicate that TGF sensitivity is enhanced during fetal life. This enhanced TGF sensitivity could in part be responsible for the increased renal vascular resistance and decreased GFR seen in the fetal kidney.