1) In which diseases are angiotensinogen levels increased?  What are the implications of this?

• As angiotensinogen level increase more of it will be converted by renin to angiotensin 1 then further converted to angiotensin 2 then the will be more of angiotensin 2. Angiotensin 2 is a potent vasoconstrictor it will cause vasoconstriction in peripheral arterioles and increase peripheral resistance resulting in an increase of blood pressure.

2)   Why do drugs which inhibit the angiotensinogen system by acting on angiotensin receptors have fewer side effects than those that inhibit ACE?

• Drugs that antagonised angiotensin are more selective therefore have less side effects compare to the ace inhibitors which are non-selective and have effect on bradykinin

3)  In which way do ACE inhibitors have a two-fold mechanism of action in the treatment of hypertension?

• By the effect of decreasing angiotensin 2 production, as a result metabolism of bradykinin does not happen these will lead to the increase of bradykinin then more vasodilation effect and also an increase of prostaglandin synthesis that cause vasodilation.

4)  At which type of angiotensin receptor do losartan and similar drugs act?  Do they have any effect, direct or indirect, at other angiotensin II receptors?

• It antagonises angiotensin 2 receptor.

5)  What are the physiological effects of kinins on arteries and veins?  Do other autacoids play a role in this action?  Explain

• Kinins act as vasodilators
• Yes autacoid do play a role nitric oxide is a potent vasodilator

6) Which receptor is probably the most involved in the important clinical effects of kinins?

• Bradykinin 2 receptor

7) In which way are natriuretic peptides possibly effective in the treatment of hypertension, as well as congestive heart failure?

• Their vasodilation effect plays a role in decreasing peripheral resistance, which decrease cardiac output as the result blood pressure decrease.

8)  What is neprylisine and what is the rationale for inhibiting its action in the treatment of heart failure? Can you name the drug being used as such? Refer to Study unit 1 where you have also come across this drug

• Neprylisine is the enzyme that metabolised ANP AND BNP
• By inhibiting neprylisine ANP and BNP will increase which will cause vasodilation which lead to decrease peripheral resistance then cardiac output.
• Sacubitril
• 9)  Give examples of endothelium-derived vasodilators and vasoconstrictors. 

• Vasoconstrictors = ET1, ET2 and ET3

  Vasodilators = PGl2. Substance P