The Angiotensin-(1-7) Axis: Formation and Metabolism Pathways

Chappell, Mark C.

The renin-angiotensin system (RAS) constitutes a key hormonal system in the physiological regulation of blood pressure via peripheral and central mechanisms. Dysregulation of the RAS is considered a major factor in the development of cardiovascular pathologies and pharmacologic blockade of this system by the inhibition of angiotensin-converting enzyme (ACE) or antagonism of the angiotensin type 1 receptor (AT(1)R) is an effective therapeutic regimen. The RAS is now defined as a more complex system composed of different angiotensin peptides with diverse biological actions mediated by distinct receptor subtypes. The classic RAS comprises the ACE-Ang II-AT(1)R axis that promotes vasoconstriction, water intake, sodium retention and increased oxidative stress, fibrosis, cellular growth, and inflammation. The non-classical or alternative RAS is composed primarily of the ACE2-Ang-(1-7)-AT(7)R pathway that opposes many actions of the Ang II-AT(1)R axis. In lieu of the complexity of this system, the chapter discusses the current evidence on the enzymatic cascade of the Ang-(1-7) axis of the RAS regarding the peptidases that contribute to the formation and degradation of the peptide in the circulation and various tissues.