Angiotensin (1-7) and other angiotensin peptides

In the classical renin angiotensin system (RAS), angiotensin II Ang IIplays many important roles in cardiovascular disease and in kidney, brain, and other organs via the Ang II type 1 receptor (AT1). The RAS consists of many angiotensin peptides, including Ang (1-7), Ang (1-9), Ang (2-8), and Ang IV. Ang (1-7), produced by angiotensin-converting enzyme 2 (ACE2), has received attention because ACE2-deficient mice have heart failure. In addition, the proto-oncogene mas and insulin regulatory aminopeptidase (IRAP) have been identified as receptors for Ang (1-7) and Ang IV, respectively, accelerating investigations into both peptides. Many groups have suggested that the ACE2/Ang (1-7)/mas axis results in beneficial effects in cardiovascular disease, renal damage, and glucose intolerance and plays an independent role in kidney disease and glucose metabolism. On the other hand, Ang IV/IRAP strongly influences memory disturbance and protects against brain ischemia. Finally, the classical RAS-ACE/Ang II/AT1 axis blockade yields beneficial effects in the context of organ damage, and additional modulation of ACE2/Ang (1-7)/mas or angiotensin IV/IRAP with this blockade results in even greater improvement. In the near future, new treatments targeting RAS and using new angiotensin peptide players might be developed for managing lifestyle-related diseases.