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

Angiotensinogen is increased in hypertension and heart failure

Implications: an increase in angiotensinogen leads to a build up of angiotensin I that is converted into angiotensin II, thus decreasing the amount of bradykinin in the body causing vasoconstriction. Which leads to raised blood pressure levels as well as urinary retention. 

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

Angiotensin antagonists selectively block the angiotensinogen system  which means that less negative effects are elicited by these drugs. Whereas ACE inhibitors are non-selective and have extra effects such as a dry cough and angioedema.

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

These inhibitors inhibit the conversion of  Angiotensin I to Angiotensin II, which will lead to a decrease in Angiotensin II production resulting in a decrease in RAAS. This decrease will mean that bradykinin can't be broken down to a metabolite, therefore it will remain a potent vasodilator =. 

A decrease in peripheral vascular resistance will follow which leads to a decrease in blood pressure. 

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 an angiotensin II receptor antagonist  (Inhibit angiotensin  AT1 receptors in heart, blood vessels, kidneys and brain) They fully block the angiotensin system (similar to ACE inhibitors but there isn't an increase in bradykinin
 

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 which increase in capillary permeability. Other autocoids do play a role in this action, but they act as second messengers such as Nitric Oxide (released after bradykinin activation)

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

Bradykinin 2 (B2) receptor

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

Natriuretic peptides are vasodilators, which means there will be a decrease in peripheral resistance and cardiac output which leads to a decrease in blood pressure. 

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 metabolises ANB and BNP.  If the activity it inhibited, the effects of ANP and BNP are prolonged which leads to vasodilation and the decrease of peripheral resistance and heart output. This leads to natriuresis and diuresis.

The drug used is Sacubitril. It can be used in combination with Valsartan which is an ACE inhibitor resulting in arterial vasodilation. The combination is used for Heart Failure. 

Give examples of endothelium-derived vasodilators and vasoconstrictors. 

vasodilators: PGI₂ & NO

vasoconstrictors: Endothelin - ET₁, ET₂, ET₃