The nonpeptide ANG-(1-7) mimic AVE 0991 attenuates cardiac remodeling and improves baroreflex sensitivity in renovascular hypertensive rats

Life Sci. 2013 Mar 12;92(4-5):266-75. doi: 10.1016/j.lfs.2012.12.008. Epub 2013 Jan 16.


Aims: The nonpeptide Ang-(1-7) analog, AVE 0991, is recognized as having beneficial cardiovascular effects similar to those induced by Ang-(1-7). In this study, we evaluated the effects of AVE 0991 on cardiovascular functions and on cardiac and renal remodeling in rats with 2K1C renovascular hypertension.

Main methods: Fisher rats underwent surgery to induce 2K1C renovascular hypertension and were then treated with AVE 0991 (1 or 3mg/kg) for 28days. At the end of treatment, the blood pressure (BP), heart rate (HR), and baroreflex sensitivity were evaluated, in conscious animals. The rats were then euthanized and the heart and kidneys removed for subsequent histological analysis.

Key findings: Treatment with AVE 0991 in 2K1C rats restored the baroreflex sensitivity of both bradycardic and tachycardic components to levels comparable to those of normotensive SHAM rats. At a higher dose (3mg/kg), AVE 0991 was also anti-hypertensive in 2K1C rats. Furthermore, AVE 0991 reduced the heart weight, thickness of myocardial fibers, number of inflammatory cells, and area of collagen deposition in the hearts of 2K1C rats compared to SHAM rats. The inflammatory process and tissue area of collagen deposition were decreased in the clipped kidney of AVE 0091-treated 2K1C rats.

Significance: Our data showed that oral treatment with AVE 0991 reduces blood-pressure cardiac remodeling and improves baroreflex sensitivity in 2K1C renovascular hypertensive rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin I / chemistry*
  • Animals
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / therapeutic use*
  • Baroreflex / drug effects*
  • Blood Pressure / drug effects
  • Collagen / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Heart Rate / drug effects
  • Hypertension, Renovascular / drug therapy*
  • Hypertension, Renovascular / metabolism
  • Hypertension, Renovascular / pathology
  • Hypertension, Renovascular / physiopathology
  • Imidazoles / administration & dosage
  • Imidazoles / chemistry
  • Imidazoles / therapeutic use*
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • Myocardium / metabolism
  • Myocardium / pathology
  • Peptide Fragments / chemistry*
  • Rats
  • Rats, Inbred F344
  • Ventricular Remodeling / drug effects*


  • AVE 0991
  • Antihypertensive Agents
  • Imidazoles
  • Peptide Fragments
  • Collagen
  • Angiotensin I
  • angiotensin I (1-7)