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 AT₁ and AT₂ receptor genes were examined using total and poly A + RNA isolated from whole Sprague-Dawley rat hearts. AT₁ mRNA 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 5 μg of poly A + RNA. AT₂ mRNA was only detectable with 20 μg of poly A + RNA. AT₂ mRNA levels were highest in the 19-day-old fetal heart with no detectable message in the 90-day-old adult heart. Qualitative PCR for AT₂ mRNA also could not detect AT₂ mRNA in the adult heart. Treatment with the AT₁ receptor 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. AT₂ blockade for 4 days with PD123319 or β-receptor blockade with propranolol for 3 weeks did not alter heart/body weights. Losartan treatment also resulted in a three-fold increase in cardiac AT₁ mRNA 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 AT₁ receptor plays a significant role in the regulation of normal cardiac growth in the young rat.