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

Autor: Mansel Harris, Allen D. Everett, A. Tufro-McReddie, Audrey Fisher
Rok vydání: 1997
Předmět:
Zdroj: Journal of Molecular and Cellular Cardiology. 29:141-148
ISSN: 0022-2828
DOI: 10.1006/jmcc.1996.0259
Popis: 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 Sprague–Dawley rat hearts. AT 1 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 μ g of poly A+RNA. AT 2 mRNA was only detectable with 20 μ 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 heart. Qualitative PCR for AT 2 mRNA also could not detect AT 2 mRNA in the adult heart. Treatment with the AT 1 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. AT 2 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 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 plays a significant role in the regulation of normal cardiac growth in the young rat.
Databáze: OpenAIRE