RAAS

Question 1

Explain the physiological role of RAAS.

Answer 1

Renin released by the JG cells converts angiotensinogen to angiotensin 1. This is then converted to ANG 2 by ACE, which is found on endothelial cells around the body. ANG2 is a potent vasoconstrictor.

• Angiotensin is binding onto AT-1.
• AT-1 receptors are GPCRs. They activate an enzyme called phospholipase C. This triggers the release of calcium in smooth muscle.
  o This enables smooth muscle contraction and vasoconstriction is achieved
• GPCRs also trigger the opening of calcium channels – allowing more calcium to enter the smooth muscle cells

Aldosterone

Question 2

What is the function of ACE inhibitors and what is an example?

Answer 2

Cilazipril. - Decrease ANG II.

ACE is involved in the breakdown of bradykinin. Bradykinin is an inflamattory molecule that leads to increase in vasodilation, sensitising in nerve terminals and vascular permeability.

• Responsible for two main adverse effects
  o Dry cough – really common. Tolerance depends on the patient.
  o Angioedema – more serious.

Question 3

Angiotensin Receptor antagonists/blockers?

Answer 3

Competitive antagonists at AT-1 receptors.
Blocks most of the activity of RAAS.
E.g. Iosartan

Question 4

ACE/ARBs or both?

Answer 4

ACE more effective but may have adverse effects, in which case use ARBs.
DO NOT use both. This is dangerous as it could cause kidney damage and hyperkalaemia.

Question 5

Aldosterone antagonists?

Answer 5

Spirinolacotne - antagonist of MC receptor. Inhibits Na+ absorption caused by aldosterone.

Question 6

Calcium channel blockers

Answer 6

Inhibit vasoconstriction.
E.g. nifedipine.

Diuretics and beta blockers.