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

  Decrease in blood pressure (hypotension). It increases blood pressure by constricting the blood vessels, it triggers thirst and the desire for salt. Increased levels of angiotensin can result in excess fluid being retained by the body.

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

The ACE inhibitors lowers blood pressure by preventing the production of Angiotensin II, while Angiotensin receptor blockers reduce the action of angiotensin II  to prevent blood vessel constriction.

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

It helps to relax the veins and arteries to lower blood pressure and it prevents an enzyme in the body from producing angiotensin II which is a substance that narrows blood vessels.

• 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?

They bind the AT1 receptor found in vascular smooth muscle and adrenal gland.

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

Kinins induce vasodilation, Increasing blood flow  throughout the body and a brief fall in blood pressure. 

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

Bradykinin displays the highest affinity for B2 ( bradykinin 2 Receptors)

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

Natriuretic Peptides may be administered as recombinant ANP, recombinant BNP or ularitide. They produce vasodilation and natriuresis and have been investigated for the treatment of congestive heart failure. Natriuretic Peptides causes vasodilation and this helps to dilate the arteries (increase in blood flow) and this leads to a fall in blood pressure and this is effective in the treatment of hypertension. 

• 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 a zinc-dependent metalloprotease and it blocks Ang II receptors. It is used to treat high blood pressure and heart failure. By blocking its action it prevents the breakdown of natriuretic peptides. Drugs are omapatrilat, sampatrilat and fasidotrilat. 

• Give examples of endothelium-derived vasodilators and vasoconstrictors.

endothelium-derived vasodilator/ endothelium-derived relaxing factor- Nitric oxide: plays a role in endothelial functions.

endothelium-derived vasoconstrictors/ endothelium-derived contracting factors- Endothelin-1 and Cox-derived thromboxane.