Structure and Synthesis

• Angiotensin II (Ang II) is an eight amino acid hormone: Asp-Arg-Val-Tyr-Ile-His-Pro-Phe.
• Produced through modifications from larger precursor molecules.
• Process initiates with angiotensinogen produced by the liver, converted to angiotensin I by renin.
• Angiotensin I is transformed into Ang II by angiotensin converting enzyme (ACE), primarily in the lungs' blood vessels.
• Renin-angiotensin system (RAS) carefully regulates cardiovascular balance.
• Other pathways for creating Ang II include enzymes like chymase in specific tissues.

Physiological Actions and Signalling

• Impacts the body through AT1 and AT2 G protein-coupled receptors.
• AT1 receptor mediates most pathological functions:
• Vasoconstriction
• Aldosterone release from adrenal glands
• Sympathetic nervous system activation
• Cell growth promotion
• AT1 receptor signaling processes:
• Activating phospholipase
• Mobilizing calcium
• Activating various protein kinase pathways
• AT2 receptor generally offsets AT1 effects by encouraging vasodilation and inhibiting cell growth.

Cardiovascular and Renal Effects

• Acts as a vasoconstrictor, raising blood pressure and increasing cardiac output.
• Promotes cardiac growth directly on heart muscle cells.
• Manages renal blood flow, filtration rate, and sodium reabsorption.
• Encourages aldosterone release, resulting in higher sodium and water retention.
• Regulates blood pressure and maintains fluid-electrolyte balance.
• Influences kidney development and repair by affecting cell growth and matrix production.

Role in Disease Pathogenesis

• Dysfunction in Ang II signaling linked to health issues:
• Hypertension with prolonged high blood pressure
• Development of heart failure due to cardiac hypertrophy, fibrosis, and remodeling
• Kidney damage, protein leakage in urine, and gradual renal function decline
• Associated with metabolic disorders, cognitive decline, and aging-related diseases.
• Prompted creation of treatment approaches focusing on RAS control.

Therapeutic Applications and Future Perspectives

• ACE inhibitors and angiotensin receptor blockers (ARBs) manage blood pressure, heart conditions, and kidney problems.
• Evaluating potential advantages of activating AT2 receptors.
• Angiotensin II's involvement in COVID-19 has attracted interest, with the virus exploiting ACE2 receptors to enter cells.
• Understanding Ang II's specific tissue actions and involvement in medical conditions can progress treatment options.
• Growing understanding of Ang II biology offers chances for developing treatments for hypertension and other diseases influenced by this peptide.