Developmental Regulation of Angiotensin Type 1 and 2 Receptor Gene Expression and Heart Growth

Little is known regarding the developmental regulation of the cardiac angiotensin type 1 (AT1) and type 2 (AT2) receptor genes or their role in normal cardiac growth. Regulation of AT1and AT2receptor genes were examined using total and poly A+RNA isolated from whole Sprague–Dawley rat hearts. AT1mRNA levels were 3.5-fold higher in the 19-day-old fetal heart compared to the 90-day-old adult as detected with 2 or 5μg of poly A+RNA. AT2mRNA was only detectable with 20μg of poly A+RNA. AT2mRNA levels were highest in the 19-day-old fetal heart with no detectable message in the 90-day-old adult heart. Qualitative PCR for AT2mRNA also could not detect AT2mRNA in the adult heart. Treatment with the AT1receptor antagonist losartan for 3 weeks in the 21-day-old rat or for 4 days in the 38-day-old rat resulted in a significant decrease in heart/body weight in both groups and body weight in the 3-week treatment group. AT2blockade for 4 days with PD123319 orβ-receptor blockade with propranolol for 3 weeks did not alter heart/body weights. Losartan treatment also resulted in a three-fold increase in cardiac AT1mRNA levels in both the 4-day and 3-week treatment groups compared to controls. We conclude that Ang II, acting primarily, if not exclusively via the AT1receptor plays a significant role in the regulation of normal cardiac growth in the young rat.