Renin-Angiotensin System

The Renin-Angiotensin System (RAS) is a critical hormonal pathway that regulates blood pressure, fluid balance, and electrolyte homeostasis. It plays a major role in kidney function and cardiovascular physiology. 

1.0What is the Renin-Angiotensin System?

The Renin-Angiotensin System is a hormone cascade that begins in the kidneys and affects the cardiovascular system. It primarily involves three components:

• Renin – an enzyme secreted by juxtaglomerular cells of the kidney.
• Angiotensin – a peptide hormone that undergoes conversion to active forms.
• Aldosterone – a hormone secreted by the adrenal cortex to regulate sodium and water balance.

The system helps maintain blood pressure, fluid balance, and electrolyte homeostasis under normal and stress conditions.

2.0Steps of the Renin-Angiotensin System

The RAAS Cascade: How It Works

The entire process is a chain reaction designed to restore normal blood pressure and fluid balance.

• Step 1: Renin Release A drop in blood pressure or blood volume is detected by the juxtaglomerular apparatus (JGA) in the kidneys. This signals the JGA to release the enzyme renin into the bloodstream.
• Step 2: Formation of Angiotensin I Once released, renin travels through the blood and acts on angiotensinogen, converting it into the inactive decapeptide, Angiotensin I.
• Step 3: Formation of Angiotensin II As Angiotensin I circulates, it reaches the lungs where it encounters Angiotensin-Converting Enzyme (ACE). ACE cleaves two amino acids from Angiotensin I, converting it into the highly active octapeptide, Angiotensin II.
• Step 4: Angiotensin II's Effects Angiotensin II is the main effector molecule of this system. It has several powerful effects that collectively raise blood pressure:
• Vasoconstriction: It is a potent vasoconstrictor, causing arterioles to narrow. This directly increases systemic vascular resistance and raises blood pressure.
• Aldosterone Release: It stimulates the adrenal cortex to secrete the hormone aldosterone.
• ADH Release: It triggers the posterior pituitary to release Antidiuretic Hormone (ADH).
• Thirst and Sodium Reabsorption: It stimulates the thirst centers in the brain and increases sodium reabsorption in the proximal convoluted tubules.
• Step 5: Aldosterone's Role Aldosterone, a mineralocorticoid hormone, acts on the distal convoluted tubules and collecting ducts of the kidneys. Its main functions are to:
• Increase sodium ion (Na+) reabsorption.
• Increase water reabsorption (following the sodium).
• Increase the excretion of potassium ions (K+). The combined effect of water and sodium reabsorption increases blood volume, which in turn raises blood pressure

3.0Renin-Angiotensin System Functions

• Maintains blood pressure under normal and hypotensive conditions.
• Regulates sodium and water balance to maintain blood volume.
• Influences glomerular filtration rate (GFR) in kidneys through vasoconstriction of efferent arterioles.
• Participates in long-term cardiovascular remodeling under chronic stress conditions.

4.0Clinical Relevance of Renin-Angiotensin System

• Hypertension: Overactivation of RAS can lead to high blood pressure.
• Heart Failure: RAS activation increases fluid retention and vascular resistance.
• Kidney Diseases: Dysfunction in RAS contributes to chronic kidney disease progression.
• Therapeutic Target:
• ACE inhibitors (e.g., Enalapril) reduce angiotensin II formation.
• ARBs (Angiotensin II Receptor Blockers) block angiotensin II receptors.
• Renin inhibitors (e.g., Aliskiren) directly reduce renin activity.

5.0Diagram of Renin-Angiotensin System