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1 Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville 3010, and 2 St. Vincent's Institute of Medical Research, Fitzroy 3065, Australia
In the adult animal, ANG-(1-7)
may counterbalance some effects of ANG II. Its effects in the
fetus are unknown. Basal ANG-(1-7), ANG I, ANG II,
and renin concentrations were measured in plasma from ovine fetuses and
their mothers (n = 10) at 111 days of gestation. In the
fetus, concentrations of ANG I, ANG-(1-7), and ANG II
were 86 ± 21, 13 ± 2, and 14 ± 2 fmol/ml,
respectively. In the ewe, concentrations of ANG I were significantly
lower (20 ± 4 fmol/ml, P < 0.05) as were
concentrations of ANG-(1-7) (2.9 ± 0.6 fmol/ml), whereas ANG II concentrations were not different (10 ± 1 fmol/ml). Plasma renin concentrations were higher in the fetus
(4.8 ± 1.1 pmol ANG
I · ml
1 · h
1) than in the
ewe (0.9 ± 0.2 pmol · ml
1 · h
1,
P < 0.05). Infusion of ANG-(1-7)
(~9 µg/h) for a 3-day period caused a significant increase in
plasma concentrations of ANG-(1-7) reaching a maximum
of 448 ± 146 fmol/ml on day 3 of infusion. Plasma
levels of ANG I and II as well as renin were unchanged by the infusion.
Urine flow rate, glomerular filtration rate, and fetal arterial blood
pressure did not change and were not different than values in fetuses
receiving a saline infusion for 3 days (n = 5).
However, the osmolality of amniotic and allantoic fluid was
significantly higher in fetuses that received
ANG-(1-7). Also, compared with the saline-infused
animals, mRNA expression levels of renin, the AT1 receptor,
and AT2 receptor were elevated in kidneys of fetuses that
received infusions of ANG-(1-7). Infusion of an
ANG-(1-7) antagonist
{[D-Ala7]-ANG-(1-7), 20 µg/h} for 3 days had no effect on fetal blood pressure or renal
function. In conclusion, although infusion of ANG-(1-7) did not affect fetal urine flow rate,
glomerular filtration rate, or blood pressure, changes in fetal fluids
and gene expression indicate that ANG-(1-7) may play
a role in the fetal kidney.
angiotensin II; kidney; renin
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