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

Hypertension and Heart failure.  Increased levels of angiotensinogen means there are more angiotensin I that can be converted into angiotensin II.  Increased levels of angiotensin I being converted into angiotensin II leads to the breakdown of bradykinin, this causes an increase in vasoconstriction.  The vasoconstriction leads to hypertension.

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

Drugs that inhibits the angiotensinogen system are more selective than ACE inhibitors.  ACE inhibitors are non-selective and also have an effect on bradykinin.  Angiotensinogen system inhibitors only inhibit the angiotensinogen system and have no effect on bradykinin so there are less side effects.   

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

ACE inhibitors decreases angiotensin II production.  Bradykinin (a potent vasodilator) can not be broken down into inactive metabolites thus it remains and increases prostaglandin synthesis and this leads to vasodilation.

The increase in the synthesis of prostaglandin leads to a decrease in PRV, and this leads to a decrease in 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 is an Angiotensin II receptor antagonist ( it blocks AT1 receptors).  They fully block the angiotensin system, but there is no increase in bradykinin.

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 of arteries and veins.  Yes, other autacoids play a role in this action, such as NO (nitric oxide) that is released after the activation of bradykinin.

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

Bradykinin 2 (B2) receptor.

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

They are effective vasodilators, thus they decreases peripheral resistance and cardiac output which leads to a decrease in blood pressure, thus it is effective in the treatment of hypertension as well as congestive heart failure.

8.) What is neprilysine and what is the rationale for inhibiting its action in the treatment of heart failure? Can you name the drug being used as such? 

Neprilysine is an enzyme that metabolizes BNP and ANP. By inhibiting neprilysine there will be an increase in ANP and BNP, thus an increase in vasodilation, this leads to a decrease in peripheral resistance and cardiac output. 

Sacubitril, it can be used with Valsartan, which is a Angiotensin II receptor antagonist.  Valsartan is used for heart failure.

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

Vasodilators : PGI2 and NO

Vasoconstrictors : ET1, ET2, ET3