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

Angiotensinogen levels are increased during pregnancy and in women taking estrogen-containing oral contraceptives. The implication of this increase is an increase in both angiotensin 2 synthesis and 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?

It is because the receptor blockers inhibit the function of angiotensin 2 by blocking the specific receptor, while ACE reduce the level of angiotensin 2 in the whole body.

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

ACE inhibitors stimulate the dilation of blood vessels by inhibiting the synthesis of angiotensin 2. ACE inhibitors also block the breakdown of bradykinin and this leads to 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?

Losartan is a selective angiotensin 2 receptor antagonist blocking at the AT1 receptors. They do not have any effect on other angiotensin 2 receptors.

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

Kinins produce marked arteriolar dilation in the heart, skeletal muscle, kidney, liver and intestine. Yes, other autacoids play a role in this action because kinins are not the only local hormones with a dilating effect. For example, histamine is released by injured tissues and cause surrounding blood vessels to dilate.

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

Kinin receptor B2.

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

Natriuretic peptides participate in the regulation of whole body metabolism. They produce vasodilation and natriuresis which is beneficial in the treatment of heart failure. The main physiological action of these peptides is decreasing arterial pressure by decreasing blood volume and systemic vascular resistance.

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 an enzyme that plays a role in the degradation of natriuretic peptides and other vasoactive peptides. Neprylisine inhibitors block the action of neprilysin and natriuretic peptide degradation is prevented. This reduces hospitalization and mortality in systolic heart failure. Example: Sacubitril/valsartan. 

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

Vasodilators: Nitric Oxide and Prostacyclin. Vasoconstrictor: Endothelin.