22nd June 2023

Effects of Angiotensin II

Angiotensin II has several mechanisms which act to increase blood pressure and blood volume:

• Vasoconstriction of arterioles
  • Angiotensin II stimulates AT1 receptors on the arteriolar vascular endothelium, thereby inducing vasoconstriction. This increases the systemic vascular resistance and, therefore, blood pressure.
• Increased sodium reabsorption in the kidneys
  • Angiotensin II increases sodium reabsorption in the PCT by increasing Na⁺/H⁺ antiporter activity and paracellular reabsorption.
• Increased noradrenaline release from the sympathetic nervous system
  • Stimulation of the sympathetic nervous system results in arteriolar vasoconstriction, increased cardiac output, and further release of renin from the JGA.
• Stimulation of ADH release from the posterior pituitary
  • Angiotensin II acts on the hypothalamus to increase thirst as well as stimulating the release of ADH from the posterior pituitary gland, reducing the loss of water in the urine and maintaining circulatory volume.
• Stimulation of aldosterone release from the adrenal cortex
  • Aldosterone is a mineralocorticoid hormone, released from the zona glomerulosa of the adrenal cortex, and acts to increase serum sodium, and thereby subsequently increase blood volume.
  • Aldosterone increases the expression of epithelial sodium channels (ENaC) on the principal cells of the late DCT and increases the activity of the basolateral membrane Na⁺-K⁺-ATPase transporters, thereby increasing sodium reabsorption from the nephron. The sodium ions in the epithelial cells are pumped into the blood by the sodium/potassium antiporter, therefore potassium is moved from the blood into the renal tubule and excreted. Therefore, increased aldosterone results in reduced serum potassium.

The Renin-Angiotensin-Aldosterone System.

Image Source: Wikimedia Commons (2018). Renin-angiotensin-aldosterone system, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Renin-angiotensin-aldosterone_system.svg (Accessed on: 11 January 2023).

ACE-inhibitors are a class of drugs which, as the name suggests, inhibit angiotensin-converting enzymes, reducing levels of angiotensin II production, and thereby reducing the actions of angiotensin II as described above. ACE-inhibitors (e.g. ramipril, lisinopril) are commonly used in the treatment of hypertension due to their action in reducing vasoconstriction of arterioles and reducing cardiac output. ACE-inhibitors are also used in renal pathology to both reduce blood pressure and proteinuria. Angiotensin II causes preferential vasoconstriction of the efferent arteriole, increasing intraglomerular pressure and GFR. Therefore, inhibition of efferent arteriolar vasoconstriction during ACE-inhibitor use reduces the GFR and reduces urinary protein excretion.