Question 5

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

[Click here to toggle visibility of the answers]

College Answer

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.

Discussion

Synthesis of angiotensin-II

  • Angiotensinogen is a large protein produced by the liver
  • Renin is a soluble protease synthesised by the juxtaglomerular cells of the renal cortex
  • Renin cleaves angiotensiongen into angiotensin-I (an inert decapeptide) and des(AngI)AGT, a large byproduct protein
  • Angiotensin-I is cleaved by ACE, producing Angiotensin-II (an active octapeptide) 

Physiological role of angiotensin

  • Angiotensin-II binds to Gq-protein coupled receptors on many tissues, producing its physiological effects via an IP3-mediated change in intracellular calcium
  • Physiological effects include:
    • Stimulating the release of vasopressin
    • Stimulating the release of aldosterone
    • Increased Na+/H+ exchange in the proximal tubules
    • Increased sensation of thirst
    • Increased sensitivity to catecholamines
  • Angiotensin-II has a 30 second half life, 

Net effects of angiotensin-II release

  • Increased sodium retention
  • Increased acid excretion
  • Increased water intake and retention
  • Peripheral vasoconstriction

Regulation of angiotensin

  • Regulated by the release of renin, which is stimulated by:
    • Systemic hypotension:
      • Afferent: baroreceptors
      • Efferent: sympethic nervous system
    • Renal hypoperfusion, sensed and responded to by juxtaglomerular cells
    • Salt depletion
      • Afferent: macula densa
      • Efferent: juxtaglomerular cells
  • Also downregulated by:
    • ANP secretion (promotes natriuresis rather than sodium retention)
    • endothelin (increases blood pressure)
    • angiotensin II (negative feedback mechanism)
    • Increased blood flow to the juxtaglomerular cells

References

Atlas, Steven A. "The renin-angiotensin aldosterone system: pathophysiological role and pharmacologic inhibition." Journal of managed care pharmacy 13.8 Supp B (2007): 9-20.

Fyhrquist, Frej, and Outi Saijonmaa. "Renin‐angiotensin system revisited." Journal of internal medicine 264.3 (2008): 224-236.

Persson, Pontus B. "Renin: origin, secretion and synthesis." The Journal of physiology 552.3 (2003): 667-671.

Lu, Hong, et al. "Structure and functions of angiotensinogen." Hypertension Research 39.7 (2016): 492-500.

Coates, David. "The angiotensin converting enzyme (ACE)." The international journal of biochemistry & cell biology 35.6 (2003): 769-773.

Busse, Laurence W., et al. "The effect of angiotensin II on blood pressure in patients with circulatory shock: a structured review of the literature.Critical Care 21.1 (2017): 324.

Rose, John C., et al. "Comparison of effects of angiotensin and norepinephrine on pulmonary circulation, systemic arteries and veins, and systemic vascular capacity in the dog." Circulation 25.1 (1962): 247-252.

Kurtz, Armin. "Control of renin synthesis and secretion." American journal of hypertension 25.8 (2012): 839-847.