Developmental regulation of angiotensin type 1 and 2 receptor gene expression and heart growth

Allen D. Everett, Audrey Fisher, Alda Tufro-McReddie, Mansel Harris

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)141-148
Number of pages8
JournalJournal of Molecular and Cellular Cardiology
Volume29
Issue number1
DOIs
StatePublished - Jan 1997
Externally publishedYes

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Keywords

  • Angiotensin II
  • Heart development
  • Losartan
  • Propranolol
  • Rat
  • mRNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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