[Active metabolites derived from angiotensin II]

Area of Science:

• Biochemistry
• Physiology
• Pharmacology

Context:

• The renin-angiotensin system (RAS) is traditionally understood to be mediated by angiotensin II (Ang II).
• Recent research reveals that degradation products of Ang II also exhibit significant biological activity.
• These peptides are generated by various enzymes, including angiotensin-converting enzyme and aminopeptidases.

Purpose:

• To explore the diverse biological functions of Ang II degradation products: Ang III, Ang IV, and Ang II (1-7).
• To identify the specific receptors and physiological roles associated with these novel peptides.
• To highlight the complexity of the RAS and its implications for therapeutic development.

Summary:

• Angiotensin III (Ang III) shares properties and receptors (AT1, AT2) with Ang II, playing a role in brain physiology and arginine vasopressin secretion.
• Angiotensin IV (Ang IV) interacts with distinct receptors, mediating effects like stimulating plasminogen activator inhibitor-1 synthesis and causing vasodilation.
• Angiotensin II (1-7) [Ang II (1-7)] acts via its own receptor (AT1-7), influences nitric oxide and prostaglandin pathways, and is involved in hydroelectrolytic balance and blood pressure regulation.

Impact:

• The discovery of multiple active peptides and receptors within the RAS significantly expands our understanding of its complexity.
• These findings challenge the conventional view of the RAS, necessitating a re-evaluation of its physiological and pathological roles.
• The identification of novel peptides and their distinct functions opens avenues for developing targeted therapeutic strategies for conditions like hypertension and glomerulosclerosis.