Angiotensin (1-7) prevent heart dysfunction and left ventricular remodeling caused by renal dysfunction in 5/6 nephrectomy mice

Hypertens Res. 2009 May;32(5):369-74. doi: 10.1038/hr.2009.25. Epub 2009 Mar 27.


The renin-angiotensin system (RAS) plays a critical role in chronic renal failure associated with heart failure. In the past few years, angiotensin (Ang) (1-7) have been reported to counteract the effects of angiotensin II (Ang II) and were even considered as a new therapeutical target in RAS. The purposes of this study were to examine whether the Ang (1-7) improves the heart function and remodeling of the left ventricle (LV) in mice with 5/6 nephrectomy (NC). We used a 5/6 nephrectomy to induce significant renal dysfunction in wildtype mice (WT). Twelve weeks after NC, WT showed high blood pressure, significant left-ventricular dilation and dysfunction, which were accompanied by cardiomyocyte hypertrophy, diffuse interstitial fibrosis and oxidative damage of cardiomyocytes. Exogenous Ang (1-7) injection improved the heart function and remodeling of LV in mice with 5/6 NC accompanied by a reduction in cardiac interstitial fibrosis, inflammatory cytokine expression and oxidative damage levels of cardiomyocytes, decrease in the profibrotic signaling molecule transforming growth factor (TGF)-beta and increase in the collagen degradation signaling molecule matrix metalloproteinase (MMP)-2, -9. However, these beneficial effects did not occur in hydralazine-treated mice. These findings suggest that (1) Exogenous Ang (1-7) injection improve the heart function and remodeling of LV in mice with 5/6 NC. (2) These beneficial effects are independent of its anti-blood pressure effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin I / therapeutic use*
  • Animals
  • Antihypertensive Agents / therapeutic use*
  • Blood Pressure / drug effects
  • Creatinine / blood
  • Heart Failure / etiology
  • Heart Failure / physiopathology
  • Heart Failure / prevention & control*
  • Heart Ventricles / pathology
  • Heart Ventricles / physiopathology
  • Kidney / physiopathology
  • Kidney Failure, Chronic / complications*
  • Kidney Failure, Chronic / physiopathology
  • Male
  • Matrix Metalloproteinase 2 / biosynthesis
  • Matrix Metalloproteinase 9 / biosynthesis
  • Mice
  • Mice, Inbred C57BL
  • Myocardium / metabolism
  • Peptide Fragments / therapeutic use*
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / biosynthesis
  • Receptors, G-Protein-Coupled / biosynthesis
  • Transforming Growth Factor beta / biosynthesis
  • Ventricular Dysfunction, Left / etiology
  • Ventricular Dysfunction, Left / pathology
  • Ventricular Dysfunction, Left / prevention & control*
  • Ventricular Remodeling / drug effects*


  • Antihypertensive Agents
  • Peptide Fragments
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Receptors, G-Protein-Coupled
  • Transforming Growth Factor beta
  • Angiotensin I
  • Creatinine
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • angiotensin I (1-7)