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

Abstract

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.

• Authors: Yiwen Li, Jianyong Wu, Qiang He, Zhangfei Shou, Ping Zhang, Wenhan Pen, Yilin Zhu, Jianghua Chen
• Journal: Hypertension research : official journal of the Japanese Society of Hypertension (Hypertens Res) Vol. 32 Issue 5 Pg. 369-74 (May 2009) ISSN: 1348-4214 [Electronic] England
• PMID: 19325560 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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)

Topics

• Angiotensin I (therapeutic use)
• Animals
• Antihypertensive Agents (therapeutic use)
• Blood Pressure (drug effects)
• Creatinine (blood)
• Heart Failure (etiology, physiopathology, prevention & control)
• Heart Ventricles (pathology, physiopathology)
• Kidney (physiopathology)
• Kidney Failure, Chronic (complications, 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, pathology, prevention & control)
• Ventricular Remodeling (drug effects)