3. Physiology
        3.12. Renal
            3.12.7. Control of sodium and water excretion
                3.12.7.4. Control of Sodium balance
3.12.7.4.1. Renin-angiotensin system

Renin-angiotensin system

[Ref: WG21:p458-p463]

Basics

Renin

Size

Other info

 

Angiotensinogen

Factors affecting circulation level

Circulating level is increased by

 

Angiotensin-converting enzyme (ACE)

Structure

Function of ACE

Angiotensins

Structure

Angiotensin I - decapeptide (10 amino acids)

Angiotensin II - 8 amino acid peptide

Angiotensin III - 7 amino acid peptide

Functions

Angiotensin I

Angiotensin III

 

Angiotensin II

Metabolism

Halflife in circulation: 1-2 minutes

Actions of angiotensin II

  1. Vasoconstriction
    * One of the most potent vasoconstrictors known
  2. Stimulate release of aldosterone
  3. Increase thirst (dipsogenic effect)
    * Via stimulation of subfornical organ (SFO)
    * Organum vasculosum of the lamina terminalis (OVLT) may also be involved
  4. Stimulate release of ACTH
  5. Stimulate release of ADH
  6. Cause contraction of mesangial cells
    --> decrease GFR
  7. Cause vasoconstriction of the arterioles
    * Efferent arteriole vasoconstriction greater than afferent arteriole [WG21:p707]
  8. Potentiation of pressor effect
    * By decreasing sensitivity of baroreflex
    * Acts on area postrema
  9. Inhibit renin secretion
    * Direct (negative) feedback to JG cells
  10. Direct effect on renal tubules to increase Na+ reabsorption
    * [WG21:p460]

Angiotensin II receptors

2 classes: AT1 and AT2

AT1 receptors
AT2 receptors

 

Regulation of renin secretion

Renin production is stimulated by

  1. Decrease in afferent arteriole BP
    * Detected by intrarenal baroreceptor (JG cells)
  2. Decrease in NaCl content in filtrate entering DCT
    * Detected by macula densa cels
  3. Stimulation of beta1-receptor on JG cells
    * Via direct stimulation by renal sympathetic nerve (main)
    * Can also due to circulating catecholamine
  4. Prostaglandins
    * Especially prostacyclin
    * Direct action on JG cells

NB:

Renin production is inhibited by

Pathological conditions causing elevated renin production

Volume-related

Renal perfusion

Others

 

Other notes

Tissue renin-angiotensin system

In addition to circulating angiotensin II, many tissues contain independent renin-angiotensin system that generate angiotensin II for local use.

Significance - UNSETTLED

Congestive heart failure

Characterised by high levels of renin, angiotensin II, aldosterone, catecholamines, and other mediators.

 

 

 



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