RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM (RAAS)
The Renin-Angiotensin-Aldosterone System (RAAS) is essentially required for regulating blood volume and systemic vascular resistance. The combined effect of these two measures influences cardiac output and arterial pressure. Renin (a proteolytic enzyme released by the kidneys into the blood circulation) facilitates angiotensin formation in blood and tissues, which further facilitates aldosterone release from the adrenal cortex.
STIMULI FOR RENIN RELEASE
Renin is released from the Juxtaglomerular (JG) cells when stimulated by:
- Increased sympathetic nerve activation (acting through β₁-adrenoceptors)
- Decreased renal artery hypotension (caused by systemic hypotension or renal artery stenosis)
- Decreased sodium delivery to the distal tubules of the kidney
Regulation of Renin Release
- Afferent Arteriole Pressure: Renin release is stimulated by decreased pressure and inhibited by increased pressure
- Sympathetic Nerve Stimulation: JG cells carry β₁-adrenoceptors which respond to sympathetic nerve stimulation by renin release
- Macula Densa: Specialised cells of distal tubules adjacent to JG cells sense Na⁺ and Cl⁻ concentration in tubular fluid
- Decreased NaCl concentration → stimulates renin release
- Increased NaCl concentration → inhibits renin release
- Prostaglandins (PGE₂ and PGI₂): Stimulate renin release in response to decreased NaCl transport across macula densa
RAAS PATHWAY
The RAAS pathway involves the following sequential steps:
- Renin Release: Kidneys release renin into blood circulation
- Angiotensinogen Conversion: Renin acts on angiotensinogen (circulating substrate from liver) → converts into decapeptide Angiotensin I by proteolytic cleavage
- ACE Action: Angiotensin-Converting Enzyme (ACE) in vascular endothelium cleaves off two amino acids → forms octapeptide Angiotensin II (can also be formed by heart, brain, and vascular tissues)
- Aldosterone Release: Angiotensin II stimulates aldosterone release from adrenal cortex
FUNCTIONS OF ANGIOTENSIN II
- Increases Systemic Vascular Resistance (SVR) and Arterial Pressure: By constricting resistance vessels (vasoconstriction)
- Increases Sodium and Water Retention: By stimulating sodium reabsorption at various sites on the renal tubule
- Stimulates Aldosterone Release: From adrenal cortex → acts on kidneys to aid sodium and fluid retention
- Stimulates ADH Release: Antidiuretic hormone from posterior pituitary gland → increases fluid retention by kidneys
- Stimulates Thirst Centers: In the brain → increases fluid intake
- Enhances Adrenergic Function: Aids release of norepinephrine from sympathetic nerve endings and inhibits its re-uptake
- Stimulates Cardiac and Vascular Hypertrophy: Long-term effects on heart and blood vessels
REGULATION OF RAAS
RAAS is regulated by:
- Mechanisms stimulating renin release (as described above)
- Natriuretic Peptides: Act as important counter-regulatory systems released by the heart (oppose RAAS effects)
SUMMARY: EFFECTS OF RAAS ACTIVATION
| Component | Effect | Result |
|---|---|---|
| Renin | Converts angiotensinogen → Angiotensin I | Initiates cascade |
| ACE | Converts Angiotensin I → Angiotensin II | Produces active hormone |
| Angiotensin II | Vasoconstriction, Aldosterone release, ADH release, Thirst stimulation | ↑ Blood pressure, ↑ Blood volume |
| Aldosterone | Sodium and water reabsorption in kidneys | ↑ Blood volume, ↑ Blood pressure |
| ADH | Water reabsorption in kidneys | ↑ Blood volume |
