Renin-angiotensin- aldesterone system (RAAS)

Question 1

Learning outcomes

Answer 1

• Describe the components of the renin angiotensin aldosterone system(RAAS)
• Discuss the role of the RAAS and Vasopressin in the maintenance of
circulatory volume and arterial blood pressure
• Describe the pharmacological classification of angiotensin receptors, their
tissue distribution and effects associated with each receptor subtype
• Explain why excessive RAAS activity could contribute to the pathogenesis of
hypertension
• List strategies for pharmacological suppression of RAAS activity

Question 2

The RAAS- features

Answer 2

• A critical regulator of blood volume and systemic vascular resistance
• Important in long-term regulation of blood pressure
• Composed of three major compounds:
• Renin (enzymatic hormone)- converst angiotensinogen in kidney to AT1, a precursor to :
• Angiotensin II (peptide hormone)
• Aldosterone (steroid hormone)

Question 3

Renin secretion

Answer 3

• Renin is secreted from the juxtaglomerular (JG) cells of afferent arterioles in the kidneys
• The rate at which renin is secreted is the primary determinant of RAS activity
1. Red. perfusion pressure of kidney detected by local baroreceptors > hypovolemia, severe dehydration, haemmhorage
2. red. Na+ detected in DCT by macula densa cells
-reduced plasma [Na+] or reduced glomerular filtration
3. Sympathetic stimulation of JGA (juxtaglomerular apparatus: JG cells and mac.den) - • E.g. stress, trauma (via β1-adrenergic receptor activation)

Question 4

Formation of angiotensin II

Answer 4

Increased renin secretion alongside increased angiotensinogen will lead to increased Angiotensin 1 (mild vasoconstrictor) production> this is converted under the influence of Angiotensin converting enzyme (ACE) in the endothelial lung capillaries> angiotensin II

Question 5

What is the role of Angiotensin II?

Answer 5

Angiotensin II is a potent vasoconstrictor which
raises peripheral resistance & blood pressure (MAP= Card.output x Peripheral resistance)
• Promotes ADH (vasopressin) release (expands EC volume and vasoconstricts)
• Promotes drinking (expands EC volume)
• Facilitates release of NE by a direct action on postganglionic sympathetic neurons
• Increases Na and H2O reabsorption from PCT

• Stimulates aldosterone release from the adrenal cortex (kidney) > to kidney in blood
• Increased Na+ and water reabsorption (expansion of EC space), and increased secretion of K+ and H+ in urine> increased blood volume-
  Angiotensin II also causes vasoconstriction of arterioles until BP returns to normal

Question 6

Angiotensin I vs II receptors

Answer 6

• AT1 Receptors
• Found on vascular smooth muscle cells (vsmc), brain, kidney, adrenal cortex
• Mediates most known effects of angiotensin II
• G-protein linked to PL-C (phospholipase c) in vascular smooth muscle cell
• Increases intracellular Ca2+ >contraction
• Activates numerous tyrosine kinases

• AT2 Receptors
• Found in fetus, expression falls after birth but are
present in brain and other organs in adult
• G-protein linked to various phosphatases
• Antagonise growth effects
• Open K+ channels
• Increase NO production

Question 7

Hypertension due to overactivity of RAAS

Answer 7

• Renin-secreting tumour
• Increased angiotensinogen production

• Renal artery stenosis

• Constriction of a renal artery by an atherosclerotic plaque
• Reduced perfusion pressure
• Secretion of renin
• BP increases

Question 8

Cardiovascular protective effects of angiotensin receptor blockers (ARBs)

Answer 8

Blockade of AT1 receptor and stimulation of AT2 receptor leads to decreased:

• VSMC proliferation
• inflammation
• oxidative stress
• fibrosis
• atherosclerosis
• vascular remodelling
• cardiac hypertrophy
• ischaemic brain damage
• insulin resistance