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 increase in proximal tubule apical membrane Na+/H+ exchanger (NHE) activity in sheep. Inasmuch as circulating angiotensin II (ANG II) levels increase immediately after birth and ANG II is known to upregulate NHE activity 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 micrograms/h) for 24 h on renal cortical NHE activity in chronically instrumented, twin ovine fetuses (129 +/- 2 days gestation, term is 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 cortices. Postinfusion plasma ANG II levels were significantly higher and plasma renin activities were significantly lower in treated fetuses compared with controls. Kinetic analysis revealed an increase in NHE activity after ANG II treatment; however, the difference was not statistically 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 mM (P = 0.11). Northern blots of total RNA from the cortices of these animals were hybridized to a D-[32P]UTP-labeled antisense RNA probe prepared from a 1.3-kb rat NHE3 cDNA fragment. There were no differences between the groups in NHE3 mRNA levels (32P counts were control 413 +/- 54, treated 340 +/- 46). ANG II does not appear to play an important role in the regulation of NHE activity in the proximal tubule of the near-term sheep fetus.
Guillery
E N
EN
Department of Pediatrics, University of Iowa, Iowa City 52242, USA.
Mathews
M S
MS
Orlowski
J
J
Robillard
J E
JE
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001158:Arteries; D001794:Blood Pressure / Q000187:drug effects; D005314:Embryonic and Fetal Development; D005260:Female; D005312:Fetal Blood / Q000187:drug effects; D005333:Fetus / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D006340:Heart Rate, Fetal / Q000187:drug effects; D007668:Kidney / Q000196:embryology; D007672:Kidney Cortex / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D012756:Sheep / Q000196:embryology; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism*
D017923:Sodium-Hydrogen Exchangers; D000804:Angiotensin II