Renin-Angiotensin System

The Renin-Angiotensin System (RAS) plays a critical role in maintaining blood pressure homeostasis, as well as fluid and salt balance in mammals. Production of angiotensins from angiotensinogen requires the participation and coordination of many proteases in different pathways. A cascade of proteolytic reactions in RAS results in the generation of different angiotensin (Ang) peptides. Renin cleaves the precursor protein, angiotensinogen, releasing the inactive peptide, angiotensin I. Subsequently, angiotensin I is cleaved by carboxypeptidases (ACE, ACE2, and CMA1), aminopeptidases (APA and APN), and endopeptidases (CTSG, NEP, THOP1 and NLN) to generate Ang peptides. Ang peptides exert diverse functions. For example, Ang II and III act as vasoconstrictors, whereas the heptapeptide Ang1-7, acts as a vasodilator. Active Ang peptides function through their respective receptors, but a single Ang peptide can induce different effects through different receptors.