Angiotensin

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Angiotensin I
Angiotensin I minimum energy conformation
Angiotensin II
Angiotensin II minimum energy conformation

Angiotensin is the group name for polypeptides with significantly different active properties which have:

  1. Key regulatory functions for blood pressure and fluid homeostasis both on a classic endocrine basis acutely but possibly more importantly chronically intracellularly in various tissues[1].
  2. Further paracrine properties such as with Angiotensin II increasing hematopoietic progenitor cell proliferation[2]
  3. Feedback properties as with angiotensin-(1-7) to the Mas G protein-coupled receptor
  4. Act as neuropeptides
    Chemical structure of Angiotensin I

Contents

Active angiotensin peptides

Active angiotensin peptides are:

  • Angiotensin I
  • Angiotensin II - Specific receptors AT1 and AT2. AT1 receptors are involved in classic actions. AT2 receptors can stimulate apoptosis, be antagonistic to AT1 receptors, allow neuronal regeneration after injury and inhibit pathological growth.
  • Angiotensin III - Angiotensin-(2-8) - no specific receptor but acts on specific Aldersterone II receptors
    • Aldosterone
    • No action on glomerular filtration rate or kidney electrolyte excretion[6]
    • Very short plasma half life
  • Angiotensin IV - Angiotensin -(3-8) - specific AT4 receptor, a M1 family transmembrane insulin-regulated aminopeptidase (IRAP) predominantly found in intracellular GLUT4 vesicles[7]
    • ↑ Renal cortical blood flow
    • ↓ Sodium transport in isolated renal proximal tubules
    • Enhance learning and memory (The peptide LVV-hemorphin 7 does too through its AT4 receptor actions)[8]
    • Proinflamatory (activates nuclear factor-kappaB(NF-kappaB)) [9]
    • Very short plasma half life
  • Angiotensin-(1-7) - Mas receptor

Endocrine actions

See Renin-Angiotensin-Aldosterone for the classic endocrine orientated description of function:

  1. Angiotensin I is enzymatically produced from angiotensinogen by renin
  2. Lung endothelium angiotensin converting enzyme converts angiotensin I to angiotensin II
  3. Angiotensin II stimulates:
    • Vasoconstriction
    • Aldosterone release from the adrenal cortex

Neuropeptide actions

These are suggested to be:[10]

  • ACE and AT1 receptors
    • Modulate central dopamine release - found in the substantia nigra, the caudate nucleus and putamen in man
  • AT4 receptors
    • Modulate central motor and sensory activities and memory - associated with cholinergic neurons
  • AT2 receptors are restricted to areas predominantly involved in the process of sensory information in adults
    • Role unclear
  • Anticonvulsant by acting at the above
    • Angiotensins II, III & IV[11]

References

  1. Stock P, Liefeldt L, Paul M, Ganten D. Local renin-angiotensin systems in cardiovascular tissues: localization and functional role. Cardiology 1995;86 Suppl 1:2-8.
  2. Oztürk MA, Güven GS, Haznedaroglu IC. How hematopoietic stem cells know and act in cardiac microenvironment for stem cell plasticity? Impact of local renin-angiotensin systems. Medical hypotheses 2004;63(5):866-74. (Direct link – subscription may be required.)
  3. Esteban V, Ruperez M, Sánchez-López E, Rodríguez-Vita J, Lorenzo O, Demaegdt H, et al. Angiotensin IV activates the nuclear transcription factor-kappaB and related proinflammatory genes in vascular smooth muscle cells. Circulation research 2005;96(9):965-73. (Direct link – subscription may be required.)
  4. Chawla LS, Busse L, Brasha-Mitchell E, Davison D, Honiq J, Alotaibi Z, Seneff MG. Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study. Critical care (London, England). 2014 Oct; 18(5):534.(Electronic) (Link to article – subscription may be required.)
  5. Khanna A, English SW, Wang XS, Ham K, Tumlin J, Szerlip H, Busse LW, Altaweel L, Albertson TE, Mackey C, McCurdy MT, Boldt DW, Chock S, Young PJ, Krell K, Wunderink RG, Ostermann M, Murugan R, Gong MN, Panwar R, Hästbacka J, Favory R, Venkatesh B, Thompson BT, Bellomo R, Jensen J, Kroll S, Chawla LS, Tidmarsh GF, Deane AM. Angiotensin II for the Treatment of Vasodilatory Shock. The New England journal of medicine. 2017 May.(Print-Electronic) (Link to article – subscription may be required.)
  6. Plovsing RR, Wamberg C, Sandgaard NC, Simonsen JA, Holstein-Rathlou NH, Hoilund-Carlsen PF, et al. Effects of truncated angiotensins in humans after double blockade of the renin system. American journal of physiology. Regulatory, integrative and comparative physiology 2003;285(5):R981-91. (Direct link – subscription may be required.)
  7. Chai SY, Fernando R, Peck G, Ye SY, Mendelsohn FA, Jenkins TA, et al. The angiotensin IV/AT4 receptor. Cellular and molecular life sciences : CMLS 2004;61(21):2728-37. (Direct link – subscription may be required.)
  8. Chai SY, Fernando R, Peck G, Ye SY, Mendelsohn FA, Jenkins TA, et al. The angiotensin IV/AT4 receptor. Cellular and molecular life sciences : CMLS 2004;61(21):2728-37. (Direct link – subscription may be required.)
  9. Esteban V, Ruperez M, Sánchez-López E, Rodríguez-Vita J, Lorenzo O, Demaegdt H, et al. Angiotensin IV activates the nuclear transcription factor-kappaB and related proinflammatory genes in vascular smooth muscle cells. Circulation research 2005;96(9):965-73. (Direct link – subscription may be required.)
  10. Saavedra JM. Brain angiotensin II: new developments, unanswered questions and therapeutic opportunities. Cellular and molecular neurobiology 2005;25(3-4):485-512. (Direct link – subscription may be required.)
  11. Tchekalarova J, Georgiev V. Angiotensin peptides modulatory system: how is it implicated in the control of seizure susceptibility? Life sciences 2005;76(9):955-70. (Direct link – subscription may be required.)