Pharmacological effects of AVE 0991, a nonpeptide angiotensin-(1-7) receptor agonist

In the last 20 years, our understanding of the physiopathology of the renin-angiotensin system (RAS) has expanded dramatically. Basic and clinical studies showed that this system includes several other components in addition to renin, angiotensin (Ang) II, an-giotensin-converting enzyme (ACE), and Ang II receptors. One of the most interesting new members of RAS is the heptapeptide Ang-(1-7). Many in vitro and in vivo studies have proven that this peptide plays several beneficial effects in the cardiovascular system, which are often opposite to the effects elicited by the main component of the RAS, Ang II. In addition, the recent discovery of the main enzyme involved in the Ang-(1-7) production, ACE2 and the description of the Ang-(1-7) receptor Mas reinforced the biological relevance of this peptide. These findings raised the possibility to develop new drugs based on the ACE2-Ang-(1-7)-Mas axis and directed to cardiovascular and -related diseases. The development of AVE 0991, a nonpeptide Ang-(1-7) receptor Mas agonist, represents an important step for exploration of the effects of Ang-(1-7) and testing of its potential as a cardiovascular drug. Among advantages of this compound in comparison with Ang-(1-7) is the fact that it is orally active and is expected to be resistant to proteolytic enzymes, circumventing an important problem associated with the use of peptides. This article briefly reviews in vitro and in vivo cardiovascular and renal effects of AVE 0991. Moreover, we are pointing to the evidence that ACE2-Ang-(1-7)-Mas axis may represent a putative target for the development of new cardiovascular drugs.