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

Hypertension

The production of angiotensinogen is increased by corticosteroids, estrogens, thyroid hormones, and ANG II.

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

ACE inhibitors block the bradykinin metabolism and thus the increase in bradykinin levels leads to a common side effect of ACE inhibitors which is a dry cough whereas Angiotensin receptor blockers do not influence bradykinin metabolism and thus no dry cough is experienced.

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

ACE inhibitors block the conversion ANG I and ANG II as well the metabolism of bradykinin to an inactive metabolite. ANG II causes an increase in Blood pressure thus by blocking the conversion of ANG I to ANG II ACE inhibitors decrease blood pressure

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?

Losartan and other similar drugs are specific competitive antagonists at angiotensin AT1 receptors

They do influence AT2 receptors when ANG II is increased

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

Kinins are potent vasodilators and increase the blood flow in the body.

Autocoids such as Histamine and Serotonin also play a role in this action.

Histamine - H1 and H2 receptors dilatate blood vessels and capillaries

Serotonin- 5-HT2receptors for vasoconstricting activity in most blood vessels and 5-HT1 for vasodilating activity

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

Beta 2 receptor

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

Natriuretic peptides increase sodium and water excretion and causes vasodilation. The excretion of sodium and water decreases volume of fluid leading to a decrease in blood pressure while the vasodilation causes blood to flow easier and thus reduces blood pressure.

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 a neutral endopeptidase responsible for degradation of natriuretic peptides in kidneys, liver, and lungs. Neprylisine inhibitors prevent the degradation of natriuretic peptides, increases ANP and BNP and causes natriuresis and and diuresis.   

A drug used as such is Sacubitril.

9. Give examples of endothelium-derived vasodilators and vasoconstrictors.

Vasodilators: Nitric oxide and PGI2

Vasoconstrictors: ET1