Question 6(p.2)
Outline the physiology of, and factors which regulate levels of angiotensin.
College Answer
For a good answer it was expected that candidates would mention the relationship of
angiotensinogen, angiotensin I, renin and Angiotensin Converting Enzyme to angiotensin II
production, the actions and fate of angiotensin II and factors that regulate angiotensin II. It
was expected that candidates mention angiotensin acts as a potent vasoconstrictor, stimulates
aldosterone secretion, facilitates noradrenaline release, preferentially vasoconstricts Efferent
arteriole in nephron, preserving GFR in low perfusion states, increases renal tubular Na+
reabsorption and increases secretion of vasopressin and ACTH.
Regulation of Angiotensin could be separated into factors increasing angiotensin levels (eg
prostaglandins, low K+ levels, Sympathetic stimulation, decreased Na+ delivery at distal
tubule, any factor contributing to reduced renal blood flow (eg hyovolaemia, cardiac failure,
renal artery stenosis) and factors reducing angiotensin levels (eg hypervolaemia, afferent
arteriolar dilatation and vasopressin).
Syllabus - N1 (h), C2b (f)
Reference: Textbook of medical Physiology, Guyton, Chp 26, Goodman and Gillman, Chp
30
Discussion
In brief, the stimuli and enzymatic steps which produce angotensin II:
Or, in the form of words:
- Properties of angiotensin-II:
- Octapeptide hormone
- Potent vasoconstrictor
- Bindins to Gq protein-coupled receptors on vascular smooth muscle facilitating an IP3- mediated increase in intracellular calcium levels, and therefore vasoconstriction
- Multiple other effects:
- Stimulates the release of aldosterone
- Stimulates the release of vasopressin
- Increases sensitivity to catecholamines
- Increases sensation of thirst
- Increases Na+/H+ exchange in the proximal tubules, thus sodium retention and acid excretion
- Biosynthesis of angiotensin-II:
- Requires the release of renin
- Renin
- 37 kDa enzyme
- Released from juxtaglomerular cells
- Is the rate-limiting step
- Cleaves angiotensiongen into angiotensin-I
- ACE
- Pulmonary enzyme
- Cleaves angiotensin-I into angiotensin-II
- Regulation of angiotensin-II release (via renin release):
- Stimulus: hypotension, hypovolemia, salt depletion, renal hypoperfusion, hypokalemia
- Sensor: arterial and renal baroreceptors; β-1 receptors on the juxtaglomerular cells
- Afferent: glossopharyngeal and vagus nerves, renal sensors of hypoperfusion (macula densa)
- Downregulation of renin secretion:
- ANP secretion (promotes natriuresis rather than sodium retention)
- endothelin (increases blood pressure)
- angiotensin II itself (negative feedback mechanism)
- Increased blood flow to the juxtaglomerular cells
References
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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.