We have previously shown in sheep that AT2 receptor mRNA expression is elevated early during fetal life and decreases rapidly near term, while AT1 receptor expression increases during the last trimester of gestation(Pediatr Res 38:896-904, 1995). The present study was designed to determine if a rise in AT1 receptor activity during fetal cardiac development regulated the decrease in AT2 receptor expression in near term fetuses.

To test this hypothesis, we studied twin fetal sheep at 95, 110, and 135d gestation (term is 145 days); one of the twins received a continuous intravenous infusion of the AT1 antagonist losartan (L) (10 mg/kg bolus followed by 20 μg/kg/min for 48 h), while the other twin served as a saline-treated control (C). L produced a significant decrease in blood pressure (BP) in 110 and 135d gestation fetuses, but not in 95d fetuses. Plasma renin activity (PRA) did not increase in 95d L-treated fetuses but rose significantly in older fetuses. Using non-parametric statistics, infusion of losartan produced significant increases in right atrial AT1 mRNA expression for all three age groups (+66±20% - 95d; +16±8% - 110d; 142±43% - 145d) and in left ventricular samples of 110d(±119±48%) fetuses. No significant changes in atrial and ventricular AT2 mRNA expression were observed at any gestational ages.

In summary, the present study demonstrates that developmental changes in AT1 receptor activity are not involved in the regulation of AT2 receptor expression during cardiac development. Furthermore, based on changes in BP and PRA, the present results suggest that AT1 receptor became functional during the last trimester of gestation in sheep.