Overview
This lecture explains the physiology and significance of the Renin-Angiotensin-Aldosterone System (RAAS) in regulating blood pressure and blood volume, its activation mechanisms, actions, and pathological consequences, especially in heart failure.
Physiology and Activation of RAAS
- RAAS is key for maintaining blood pressure and blood volume, especially during hypotension (e.g., hemorrhage).
- Reduced renal perfusion (less blood flow to kidneys) stimulates renin release from specialized kidney cells.
- Each nephron has a juxtaglomerular apparatus, consisting of baroreceptors (pressure sensors) and macula densa (sodium sensors).
- Baroreceptors (juxtaglomerular cells) sense low blood flow and release renin.
- Macula densa senses low sodium, further stimulating renin release.
- Sympathetic nervous system activation (via beta-1 receptors) also increases renin release during low blood pressure.
Cascade and Actions of RAAS
- Renin converts angiotensinogen (from liver) to angiotensin I.
- Angiotensin I is converted to angiotensin II by ACE (angiotensin converting enzyme) on pulmonary capillary endothelial cells.
- ACE also inactivates bradykinin, a vasodilator, thereby enhancing vasoconstriction.
- Angiotensin II constricts veins (increases venous return and preload) and arterioles (raises afterload and diastolic pressure), increasing systolic and diastolic BP.
- Angiotensin II stimulates adrenal cortex (zona glomerulosa) to release aldosterone.
Actions of Aldosterone and ADH
- Aldosterone acts on principal cells in nephron to increase sodium and water reabsorption, and potassium excretion.
- Aldosterone increases sodium-potassium ATPase and sodium channel expression, enhancing sodium (and water) retention.
- Angiotensin II stimulates hypothalamus to release ADH (vasopressin) from posterior pituitary, increasing water reabsorption in the kidney's distal nephron.
Additional Effects of Angiotensin II
- Angiotensin II stimulates thirst and increases central sympathetic outflow.
- Enhances norepinephrine release and action at target tissues, amplifying vasoconstriction and renin release.
Pathological Aspects: Heart Failure & Cardiac Remodeling
- Chronic activation of RAAS (e.g., in heart failure) leads to constant high angiotensin II and aldosterone.
- Causes pathological hypertrophy and fibrosis (remodeling) of myocardium, worsening cardiac function.
- Also contributes to vascular changes (vasculopathies).
Key Terms & Definitions
- RAAS — Renin-Angiotensin-Aldosterone System: regulates blood pressure/volume.
- Renin — Enzyme from kidneys; starts the RAAS cascade.
- Juxtaglomerular apparatus — Nephron structure sensing pressure (baroreceptors) and sodium (macula densa).
- Angiotensinogen — Liver protein, precursor to angiotensin I.
- Angiotensin I/II — Vasoconstrictive peptides, II being more potent.
- ACE — Angiotensin Converting Enzyme: converts I to II, inactivates bradykinin.
- Aldosterone — Adrenal cortex hormone; retains Na+/water, excretes K+.
- ADH (vasopressin) — Pituitary hormone that increases kidney water reabsorption.
- Cardiac remodeling — Structural changes in heart muscle due to chronic RAAS activation.
Action Items / Next Steps
- Review drugs affecting RAAS, especially ACE inhibitors and angiotensin receptor blockers, in the next session.