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

Increased levels of angiotensinogen are associated with a condition of essential hypertension.

These levels are increased by glucocorticoids, oestrogens, thyroid hormone, and angiotensin II.

Therefore, this explains the increase

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

ACE inhibitors may cause a dry cough and angioedema due to the increased levels of bradykinin, because angiotensinogen receptor blockers do not influence bradykinin there is little to no dry cough as a side effect

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

It Prevents the conversion of Angiotensin I to angiotensin II, thus inhibiting the release of aldosterone. Therefore, the action of ACE inhibitors to inhibit bradykinin and other substances contributes to lowering the 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?

The drugs act at AT1 receptors and when ANG II is increased, they act on the AT2 receptors.

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

Kinins cause vasodilation on arteries due to the direct inhibitory effect of kinins on arteriolar smooth muscle or it is mediated by the release of nitric oxide or vasodilator prostaglandins such as PGE2 and PGI2. Kinins cause the veins to contract due to direct stimulation of venous smooth muscle or from the release of vasoconstriction prostaglandins PGF 2 alpha. Autacoids such as bradykinin play a role as bradykinin is a potent vasodilator.

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

Type b2 receptor

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

Natriuretic peptides lead to the following physiological occurrences: Increased renin production, increased ANG2, vasodilation and natriuresis

• 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 that cleaves peptides at the amino side of hydrophobic residues and inactivates several peptide hormones including glucagon, enkephalins, substance P, neurotensin, oxytocin, and bradykinin.

The rationale of inhibiting them is to ensure an increase in the systemic concentration of the Natriuretic peptides and so ensure that their physiological effects are effective

• Give examples of endothelium-derived vasodilators and vasoconstrictors. 

Vas0dilator nitric oxide and PGI2

Vasoconstrictor ET1 and receptor subtypes ETA and ETB