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

-  Hypertension and heart failure , Increased levels of angiotensinogen increases the amount of angiotensin I that can be converted into angiotensin II, thus decreasing the amount of bradykinin in the body, which causes an increase in vasoconstriction. 

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

- The angiotensin blockers are also more selective than the non-selective ACE inhibitors, thus it will have less effects since the non-selective ACE inhibitors.

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

- ACE inhibitors block the conversion of ANG I to ANG II as well as inhibits the degradation of other substances for example enkephalins, bradykinin and substance P.

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

- They act on AT1 receptors and when ANG II is increased, they act on the AT2 receptors.

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

- Kinins cause vasodilation on arteries due to the direct inhibitory effect of kinins on arterial smooth muscle and is mediated by the release of nitric oxide, vasodilation prostaglandins such as PGE 2 and PGI2.

6.Which receptor is probably most involved in the important clinical effects of Kinins?

- B2 receptors.

7. in which way do natriuretic peptides possibly effective in the treatment of hypertension, as well as congestive heart failure? 

- Natriuretic peptides lead to  the following physiological occurrences: Increased renin production, increased ANG2, vasodilation and natriuresis.

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.

- Neprilysin is the catalytic enzyme that break down the Natriuretic peptides to their metabolites and so inactivate them. The rationale of inhibiting them is to ensure an increase in the systemic concentration of the Natriuretic peptides and so ensure that their physiological effects are effective.

9.Give examples of endothelium derived Vasodilators and vasoconstrictors.

Vasodilators: nitric oxide and PG I2

Vasoconstrictors: ET1 and receptor subtypes ETA and ETB.