ANGIOTENSIN-II AND THE MATURATION OF RENAL CORTICAL NA+ H+ EXCHANGER ACTIVITY DURING FETAL LIFE IN SHEEP/

The postnatal rise in renal Na+ reabsorption is associated with an inc rease in proximal tubule apical membrane Na+/H+ exchanger (NHE) activi ty in sheep. Inasmuch as circulating angiotensin II (ANG II) levels in crease immediately after birth and ANG II is known to upregulate NHE a ctivity in the adult proximal tubule, we postulated that ANG II plays a role in mediating maturational changes in NHE activity. We therefore studied the effects of ANG II infusion (10 mu g/h) for 24 h on renal cortical NHE activity in chronically instrumented, twin ovine fetuses (129 +/- 2 days gestation, terms 145 days, n = 10 pairs); one twin of each pair served as a control. After 24 h, the fetuses were killed and brush-border membrane vesicles (BBMV) were prepared from the renal co rtices. Postinfusion plasma ANG II levels were significantly higher an d plasma renin activities were significantly lower in treated fetuses compared with controls. Kinetic analysis revealed an increase in NHE a ctivity after ANG II treatment; however, the difference was not statis tically significant: maximal velocity (in nmol . s(-1). mg protein(-1) ) control 1.65 +/- 0.50, treated 2.31 +/- 0.66 (P = 0.11, n = 9 pairs) ; Michaelis constant control 8.29 +/- 1.17 mM, treated 9.84 +/- 1.26 m M (P = 0.11). Northern blots of total RNA from the cortices of these a nimals were hybridized to a D-[P-32] UTP-labeled antisense RNA probe p repared from a 1.3-kb rat NHE3 cDNA fragment. There were no difference s between the groups in NHE3 mRNA levels (P-32 counts were control 413 +/- 54, treated 340 +/- 46). ANG II does not appear to play an import ant role in the regulation of NHE activity in the proximal tubule of t he near-term sheep fetus.