Is the renin-angiotensin system actually hypertensive?

Area of Science:

• Cardiovascular Physiology
• Endocrinology
• Renal Physiology

Background:

• The traditional view of the renin-angiotensin system (RAS) focuses on its role as an endocrine hypertensive system driven by angiotensin II.
• Recent discoveries reveal new angiotensins and receptors, many with hypotensive and natriuretic effects, such as angiotensin-(1-7) and its receptor Mas.
• Renin and pro-renin interact with a common receptor, influencing intracellular effects beyond angiotensin II production.

Purpose of the Study:

• To explore the expanded complexity of the renin-angiotensin system (RAS).
• To highlight novel pathways and local regulatory mechanisms within the RAS.
• To emphasize the need for an evolving concept of RAS that incorporates its dual hypertensive and hypotensive potentials.

Main Methods:

• Review of historical and recent literature on the renin-angiotensin system.
• Analysis of newly described angiotensins, receptors, and pathways.
• Examination of local and systemic regulatory mechanisms, including intrarenal and urinary RAS.

Main Results:

• The RAS includes hypotensive pathways like angiotensin-(1-7) acting via the Mas receptor.
• A novel renin-independent pathway involves angiotensin-(1-12) conversion.
• Local RAS in vessels and organs, independent renal vascular RAS, and urinary RAS play significant roles.
• Renalase acts antagonistically to renal RAS effects.
• Calcium homeostasis is critical for renin production.

Conclusions:

• The concept of the RAS must expand beyond its traditional hypertensive role.
• The RAS possesses dual functionalities, capable of both increasing and decreasing blood pressure.
• Local and systemic interactions, including novel pathways and counterbalancing mechanisms, are essential for understanding RAS physiology.