Angiotensin II Type 1 (AT1) Receptor Expression and Regulation in Human Fetal Lung In Vitro 305

Abstract

Specific angiotensin II (ANG II) receptors are present early in gestation and may play a role in organ growth and development. To investigate regulation of the AT1 receptor in human lung, we first characterized changes in AT1 mRNA levels in midtrimester human fetal lung explants, which spontaneously differentiate in culture. Northern blot analysis revealed that during four days in explant culture in serum-free medium, AT1 mRNA levels decreased to 19±3, 10±3, 8±2 and 5±2% (days 1, 2, 3, 4, respectively, all p<0.05) of control levels (day 0). The decrease in AT1 mRNA after 48 h in culture also occurred in the presence of 5% fetal calf serum. Immunostaining demonstrated a mesenchymal distribution of the AT1 receptor with limited expression in vascular smooth muscle. AT1 mRNA levels were unaltered after 48 h in culture with ANG II (10-5 to 10-9 M), the AT1 receptor antagonist losartan (10-5 to 10-9 M), or cortisol (10-6 and 10-9 M). Finally, abundance of AT1 mRNA was similarly decreased by incubation in 2% or 20% oxygen. These findings indicate that AT1 mRNA and protein are present in midtrimester fetal lung and that AT1 mRNA levels decrease in association with spontaneous differentiation of human fetal lung in vitro. AT1 mRNA in human fetal lung explants is not regulated by ligand, receptor antagonist, cortisol, or oxygen.