Renal and cardiovascular responses to an intravenous infusion of ANG II (1 microg/h) or saline for 3 days were examined in ovine fetuses at midgestation (75-85 days of gestation, term 150 days). ANG II caused an increase in fetal blood pressure (36 +/- 2 to 44 +/- 3 mmHg) and urine flow rate (8 +/- 2 to a maximum of 18 +/- 6 ml/h). Plasma renin concentrations decreased in ANG II-infused fetuses. Fetal fluids (amniotic and allantoic) did not differ in volume or composition between the groups when measured at postmortem. There was no difference in the expression levels of the mRNA for the angiotensin (AT(1) or AT(2)) receptors between the two groups when measured by an RNase protection assay. However, there was a significant decline in renin and AT(1) receptor gene expression when measured by a real-time polymerase chain reaction method. These results indicate that ANG II is diuretic and pressor when infused at midgestation. ANG II can feedback to decrease renin secretion by the fetal kidney, and this may occur by decreased renin gene expression.