Prevention of angiotensin II-induced cardiac remodeling by angiotensin-(1-7)

Am J Physiol Heart Circ Physiol. 2007 Feb;292(2):H736-42. doi: 10.1152/ajpheart.00937.2006. Epub 2006 Nov 10.


Cardiac remodeling, which typically results from chronic hypertension or following an acute myocardial infarction, is a major risk factor for the development of heart failure and, ultimately, death. The renin-angiotensin system (RAS) has previously been established to play an important role in the progression of cardiac remodeling, and inhibition of a hyperactive RAS provides protection from cardiac remodeling and subsequent heart failure. Our previous studies have demonstrated that overexpression of angiotensin-converting enzyme 2 (ACE2) prevents cardiac remodeling and hypertrophy during chronic infusion of angiotensin II (ANG II). This, coupled with the knowledge that ACE2 is a key enzyme in the formation of ANG-(1-7), led us to hypothesize that chronic infusion of ANG-(1-7) would prevent cardiac remodeling induced by chronic infusion of ANG II. Infusion of ANG II into adult Sprague-Dawley rats resulted in significantly increased blood pressure, myocyte hypertrophy, and midmyocardial interstitial fibrosis. Coinfusion of ANG-(1-7) resulted in significant attenuations of myocyte hypertrophy and interstitial fibrosis, without significant effects on blood pressure. In a subgroup of animals also administered [d-Ala(7)]-ANG-(1-7) (A779), an antagonist to the reported receptor for ANG-(1-7), there was a tendency to attenuate the antiremodeling effects of ANG-(1-7). Chronic infusion of ANG II, with or without coinfusion of ANG-(1-7), had no effect on ANG II type 1 or type 2 receptor binding in cardiac tissue. Together, these findings indicate an antiremodeling role for ANG-(1-7) in cardiac tissue, which is not mediated through modulation of blood pressure or altered cardiac angiotensin receptor populations and may be at least partially mediated through an ANG-(1-7) receptor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Angiotensin I / metabolism*
  • Angiotensin I / pharmacology
  • Angiotensin II / analogs & derivatives
  • Angiotensin II / pharmacology
  • Animals
  • Blood Pressure / drug effects
  • Cardiomegaly / etiology
  • Cardiomegaly / metabolism*
  • Cardiomegaly / pathology
  • Cardiomegaly / physiopathology
  • Cardiomegaly / prevention & control
  • Disease Models, Animal
  • Fibrosis
  • Heart / drug effects
  • Hypertension / chemically induced
  • Hypertension / complications
  • Hypertension / physiopathology
  • Male
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Peptide Fragments / metabolism*
  • Peptide Fragments / pharmacology
  • Proto-Oncogene Proteins / drug effects
  • Proto-Oncogene Proteins / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Angiotensin, Type 1 / metabolism
  • Receptor, Angiotensin, Type 2 / metabolism
  • Receptors, G-Protein-Coupled / drug effects
  • Receptors, G-Protein-Coupled / metabolism*
  • Time Factors
  • Transforming Growth Factor beta / blood
  • Ventricular Remodeling* / drug effects


  • 7-Ala-angiotensin (1-7)
  • Peptide Fragments
  • Proto-Oncogene Proteins
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Receptors, G-Protein-Coupled
  • Transforming Growth Factor beta
  • proto-oncogene proteins c-mas-1
  • Angiotensin II
  • Angiotensin I
  • angiotensin I (1-7)