Question 5

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

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