Renin-angiotensin system revisited

Area of Science:

• Physiology
• Endocrinology
• Cardiovascular Research

Background:

• The classical renin-angiotensin system (RAS) primarily involved circulating renin, angiotensinogen, angiotensin I, angiotensin II (Ang II), and angiotensin-converting enzyme (ACE).
• Ang II was considered the main effector, acting via AT1 and AT2 receptors as a circulating hormone.
• The importance of RAS in cardiovascular disease is underscored by the success of ACE inhibitors and AT1 receptor blockers.

Purpose of the Study:

• To explore the expanded view of the renin-angiotensin system (RAS) beyond its classical endocrine functions.
• To highlight the identification of local tissue RAS, intracellular RAS, and novel RAS peptides and receptors.
• To discuss the implications of these discoveries for understanding RAS complexity and its physiological roles.

Main Methods:

• Review of existing literature on the renin-angiotensin system (RAS).
• Analysis of recent discoveries regarding local tissue RAS, intracellular RAS, and novel peptides/receptors.
• Synthesis of findings to present an updated, multilayered view of RAS.

Main Results:

• Identification of local tissue RAS in most organs and evidence for intracellular RAS.
• Discovery of additional RAS peptides (Ang III, Ang IV, Ang 1-7) with distinct actions and receptors (IRAP, Mas).
• Emergence of new components like ACE2 and renin receptors, significantly increasing RAS complexity.

Conclusions:

• The RAS is not limited to endocrine functions but also operates via paracrine and intracrine pathways.
• The RAS comprises a complex network of peptides, enzymes, and receptors, regulating diverse physiological functions.
• Ongoing research into RAS components, including renin inhibitors, holds great promise for understanding and treating various conditions.