Study Notes – Renin-Angiotensin-Aldosterone System (RAAS)

Overview

• Kidneys control long-term blood pressure via RAAS.

• Important for understanding antihypertensive drugs.

• Blood filtration by kidneys: ~120 mL/min → ~180 L/day (most reabsorbed, ~1.8 L urine).

Why Kidneys Control BP

• Constantly filter blood → sensitive to blood pressure (BP) and blood volume (BV) changes.

• Drop in BP/BV → triggers mechanisms to restore filtration and BP.

Key Players in the Kidney

Nephron

• Functional unit of kidney; ~1 million per kidney.

• Glomerulus: capillary “ball” inside Bowman’s capsule → filtration occurs.

• Afferent arteriole: blood enters → has smooth muscle, can sense BP.

• Efferent arteriole: blood leaves → constriction affects filtration.

Cells

1. Juxtaglomerular (JG) / Granular / Renin-Secreting Cells

   • Baroreceptors in afferent arteriole.

   • Detect BP drop → release renin.

2. Macula Densa Cells

   • In distal convoluted tubule → detect low sodium (Na⁺).

   • Signal JG cells to release renin.

3. Mesangial Cells

   • Facilitate communication between macula densa and JG cells.

 Three Major Triggers for Renin Release

1. Intra-renal baroreceptors: BP drop in afferent arteriole → renin release.

2. Macula densa sodium sensing: Low Na⁺ in distal convoluted tubule → renin release.

3. Sympathetic stimulation (most prominent):

   • Baroreceptors in carotid sinus/aortic arch sense low BP → sympathetic NS → β1 receptors on JG cells → renin release.

RAAS Cascade

1. Renin → enzyme released by JG cells.

2. Angiotensinogen → produced by liver, inactive.

3. Renin + Angiotensinogen → Angiotensin I (still inactive).

4. Angiotensin-Converting Enzyme (ACE) → converts Angiotensin I → Angiotensin II (active).

 Actions of Angiotensin II

1. Vasoconstriction → ↑ systemic vascular resistance → ↑ BP.

2. Constricts efferent arteriole → ↑ glomerular filtration rate (GFR).

3. Stimulates aldosterone release from adrenal cortex → mineralocorticoid.

   • Aldosterone: increases sodium reabsorption in distal tubule & collecting duct → water follows → ↑ blood volume → ↑ BP.

4. Stimulates ADH (vasopressin) release → increases water reabsorption in distal tubule & collecting duct.

5. Activates thirst & salt appetite centers → behavioral response to restore blood volume.

Key Drugs Targeting RAAS

Drug Class	Mechanism	Examples	Effect
ACE inhibitors	Block ACE → ↓ Angiotensin II	Lisinopril	↓ vasoconstriction, ↓ aldosterone, ↓ BP
ARBs (Angiotensin II Receptor Blockers)	Block Angiotensin II receptor	Losartan	Prevent vasoconstriction & aldosterone effects
Mineralocorticoid Receptor Antagonists (MRAs)	Block aldosterone receptor	Spironolactone	↓ Na⁺ reabsorption → ↓ water → ↓ BP
Direct Renin Inhibitors	Inhibit renin	Aliskiren	Prevents formation of Angiotensin I → ↓ BP

Key Concepts

• BP = Cardiac Output × Systemic Vascular Resistance.

• Kidney regulates both BP and blood volume via RAAS.

• Sodium reabsorption → water follows → increases blood volume & BP.

• Angiotensin II = central regulator: vasoconstriction + aldosterone + ADH + thirst.