U1vi / 21B05: Write detailed notes on angiotensin, including its synthesis, role within the body and regulation

21B05: Exam Report

Write detailed notes on angiotensin, including its synthesis, role within the body and regulation

24% of candidates passed this question.

This question provided headings for the answer template. Good answers integrated the required facts from the appropriate chapters of the major texts. Most answers lacked detail surrounding the factors that increase or decrease angiotensin activity. Few answers provided any detail as to all the mechanisms through which angiotensin exerts it effects. A lot of answers focussed singularly on the vascular effects of angiotensin. Overall, there was often a paucity of detail, with vague statements and incorrect facts.

U1vi / 21B05: Write detailed notes on angiotensin, including its synthesis, role within the body and regulation

NB

Technically not a renal hormone but parked in U1vi with RAAS

Definition

  • Angiotensinogen is a peptide hormone (α2 globulin) produced in liver.

Synthesis

  1. Angiotensin 1
    • ↑ Renin by JGA → cleavage of Angiotensinogen → AT1
    • No biological activity
    • Rate limiting step of the RAAS pathway
  2. Angiotensin 2
    • An active 8 a.a peptide
    • ACE in pulmonary capillary endothelium converts AT1 → ↑AT2
  3. Angiotensin 3
    • AIII has similar actions to AII, but with much less potency (40% of the pressor activity AT2)
    • 100% of the aldosterone-producing activity
    • Additional a.a. moieties are split from AII to produce AIII in some tissues
  4. Angiotensin 4
    • Minimal biological activity

Role within the body

  • Acts via GPCR (Gq via PLC to increase IP3 and intracellular Ca)
  • CVS
    • Vasopressor: Potent vasoconstrictor → ↑ BP 2° to ↑ SVR
    • Resets baroreceptor control of HR at higher pressure
    • Potent mitogen for smooth muscle and cardiac myocytes
    • Direct positive inotrope
  • CNS
    • ↑ sympathetic outflow: via central and peripheral effects → ↑ HR, C.O., BP
    • ↑ thirst/water intake via hypothalamus
    • ↑ ADH release from posterior pituitary.
    • Hence increase body water content
  • Renal
    • Negative feedback on renin release
    • ↑ renal tubular reabsorption of Na+ and Cl– (and ↑ ECVF) and ↑ tubular K+ secretion via → (i) Direct effects on the PCT, and (ii) Release of Aldosterone from the adrenal cortex
    • ↓ RBF and GFR (esp at ↑↑↑ levels of AII) via:
      1. Renal afferent and efferent arteriolar vasoconstriction (↓ GFR and RBF)
      2. Mesangial contraction (↓ Kf and GFR)
    • Direct renal arteriole constriction (efferent = afferent)
    • Direct effect and via ↑ aldosterone release
    • Net tubular fluid/electrolyte reabsorption → due to ↓ peritubular capillary PHYDROSTATIC 2° to renal arteriolar

 

ATII – t ½ ~ 1-3 mins

Regulation

Factors which alter renin release cause a corresponding change in angiotensin 2.

  • Stimulation of renin secretion (↑ renin → ↑ angiotensin 2)
    • β-1 agonism
    • ↓ renal perfusion pressure (flow (eg hyovolaemia, cardiac failure, renal artery stenosis)
    • ↓ sodium delivery to DCT
    • Prostaglandins
  • Inhibition or renin secretion (↓ renin → ↓ angiotensin 2):
    • ↑ renal perfusion pressure (via afferent arteriolar dilatation) [eg: (eg hypervolaemia, afferent arteriolar dilatation and vasopressin)
    • ↑ sodium delivery to DCT
    • ↑ by angiotensin II (negative feedback) and vasopressin

Author: Huiling Tan