Upregulation of angiotensin-converting enzyme 2 by all-trans retinoic acid in spontaneously hypertensive rats

Hypertension. 2004 Dec;44(6):907-12. doi: 10.1161/01.HYP.0000146400.57221.74. Epub 2004 Oct 11.


There is increasing evidence that all-trans retinoic acid (atRA) influences gene expression of components of renin-angiotensin system (RAS), which plays a pivotal role in the pathophysiology of essential hypertension. To further validate effects of atRA on the RAS and to assess the possibility that atRA affects the activity of angiotensin-converting enzyme 2 (ACE2), gene, and protein expression of ACE2 have been examined by real-time polymerase chain reaction and Western blot methods in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Rats were treated with atRA (10 or 20 mg x kg(-1) x day(-1)) or placebo given as daily intraperitoneal injection for 1 month. ACE2 expression was markedly decreased in placebo-treated SHR when compared with WKY rats. However, in atRA-treated SHR, a significant upregulation of ACE2 expression was observed in heart and kidney. In conclusion, chronic atRA treatment increases gene and protein expressions of ACE2, resulting in the reduction of blood pressure and the attenuation of myocardial damage in SHR, which suggests that atRA may be an attractive candidate for the potential prevention and treatment of human essential hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Animals
  • Blood Pressure / drug effects*
  • Carboxypeptidases / genetics
  • Carboxypeptidases / metabolism*
  • Kidney / metabolism*
  • Male
  • Myocardium / metabolism*
  • Myocardium / ultrastructure
  • Peptidyl-Dipeptidase A
  • RNA, Messenger / analysis
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Tretinoin / pharmacology*
  • Up-Regulation / drug effects


  • RNA, Messenger
  • Tretinoin
  • Carboxypeptidases
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Ace2 protein, rat
  • Angiotensin-Converting Enzyme 2