DEVELOPMENTAL REGULATION OF ANGIOTENSIN TYPE-1 AND TYPE-2 RECEPTOR GENE-EXPRESSION AND HEART GROWTH

Little is known regarding the developmental regulation of the cardiac angiotensin type 1 (AT(1)) and type 2 (AT(2)) receptor genes or their role in normal cardiac growth. Regulation of AT(1) and AT(2) receptor genes were examined using total and poly A + RNA isolated from whole S prague-Dawley rat hearts. AT(1) mRNA levels were 3.5-fold higher in th e 19-day-old fetal heart compared to the 90-day-old adult as detected with 2 or 5 mu g of poly A + RNA. AT(2) mRNA was only detectable with 20 mu g of poly A + RNA. AT(2) mRNA levels were highest in the 19-day- old fetal heart with no detectable message in the 90-day-old adult hea rt. Qualitative PCR for AT(2) mRNA also could not detect AT(2) mRNA in the adult heart. Treatment with the AT(1) receptor antagonist losarta n for 3 weeks in the 21-day-old rat or for 4 days in the 38-day-old ra t resulted in a significant decrease in heart/body weight in both grou ps and body weight in the 3-week treatment group. AT(2) blockade for 4 days with PD123319 or beta-receptor blockade with propranolol for 3 w eeks did not alter heart/body weights. Losartan treatment also resulte d in a three-fold increase in cardiac AT(1) 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 AT(1) receptor p lays a significant role in the regulation of normal cardiac growth in the young rat. (C) 1997 Academic Press Limited.