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

They are increased by estrogens, corticosteroids, thyroid hormones and ANG II. However, these levels are increased when women take estrogen from oral contraceptives and during pregnancy. Therefore explaining the raised angiotensinogen concentration which may result in hypertension. 

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

Since there is an increase in the levels of bradykinin, ACE inhibitors can lead to angioedema and a dry cough.

Question 3: In which way does ACE inhibitors have a two-folded mechanism of action in the treatment of hypertension?

ACE inhibitors block the conversion of ANG I to ANG II. They also prevent the breakdown of substances namely, enkephalins, bradykinin and substance P. The Action of ACE inhibitors which hinders substances like bradykinin and contributes to lowering blood pressure. 

Question 4: At which type of angiotensin receptor does Losartan and similar drugs act? Do they have any effect, direct or indirect, at other angiotensin II receptors?

Drugs act on  AT1 receptors and when ANG II is increased they act on AT2 receptors. 

Question 5: What are the physiological effects of kinins on arteries and veins? Do other autacoids play a role? Explain

They cause vasodilation in the arteries, this is because of the direct inhibitory effect of kinins on the arteriolar smooth muscle. It can also be explained by the release of vasodilator prostaglandins (PGE2 and PGI2) or NO. Kinins cause the vein to contract because of the release of vasoconstriction prostaglandins (PGF2 alpha) or the direct stimulation of the venous smooth muscle. Autacoids like bradykinin is a potent vasodilator. 

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

B2 receptor.

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

Natriuretic peptides (namely, ularitide, carperitide, nesiritide and urodilatin) causes natriuresis and vasodilation in the treatment of congestive heart failure. 

Question 8: what is neprylisin and what is the rationale for inhibiting its action in the treatment of heart failure? can you name the drug being used for such? 

It is a key enzyme in the breakdown of natriuretic peptides. The initial motive of neprylisin in cardiovascular disease was to increase endogenous natriuretic peptide levels, therefore achieving vasodilation and natriuresis.

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

• Vasodilator: PGI2 and Nitric oxide.
• Vasoconstrictors: ET1 and the receptor subtypes ETA and ETB.