1.What do you understand by the term “endothelium-dependent” vasodilation?  Explain?

the term “endothelium-dependent” vasodilation means the endothelium controls vascular tone in a paracrine fashion through releasing diffusible soluble mediators that can act on physically contiguous cells.

2. When we talk about the NOS enzyme, what is meant by “constitutive” and “inducible” enzymes and what are the pathological and physiological implications thereof?

when exposed to inflammatory mediators iNOS are expressed through transcriptional induction which means NO synthesis is not regulated by calcium. eNOS and nNOS’s NO synthesis is dependent on calcium regulation as they are expressed continuously produced regardless of cells' needs (constitutive). complexes between calmodulin and Cytosolic calcium form which then binds and activates eNOS and nNOS.

3.Explain how NO contributes to fatal pathology of septic shock

Components which are present in bacteria such as endotoxins and cytokines cause the formation of iNOS in smooth muscle cells and macrophages. It is a systemic inflammatory response to an infection. The accumulation formation of nitric oxide in a large area results in shock and severe hypertension which can be fatal.

4.Which autacoids mechanism of action depends on effects on the guanylyl cyclase-cGMP system

Nitric oxide

5.NO may be toxic to the cell.  Which mechanisms are available to the body to counter this detrimental effect of NO?

Homeostasis counters the detrimental effect.

6.Name a way in which NO can act pro-inflammatory. Give examples where it will have advantages or disadvantages.

when there is an overproduction in abnormal conditions it induces inflammation and thus a acts as a pro-inflammatory this is advantageous as inflammation increases blood flow to the affected area thus speeding up the rate of healing of injured tissue then again it can result in pain of a swollen joint when it is used which can be discomforting.

7. In what possible neurological and mental illnesses is NO involved?

Alzheimer's, Huntington's disease, Parkinsonism,

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

Production of angiotensinogen is increased by ANG II, corticosteroids, estrogens and thyroid hormones. which during pregnancy It is further elevated. Resulting in increased plasma angiotensinogen concentration which then leads to hypertension.

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

Angiotensinogen receptor blockers do not have an effect on bradykinin there is little to no side effects.

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

ACE inhibitors block the conversion of ANG I to ANG II and also inhibit the degradation of other substances such as substance P and enkephalins. This inhibitory effects 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 act on the AT2 receptors with ANG II presence

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

cause vasodilation on arteries due to the direct inhibitory effect on arteriolar smooth muscle or it is mediated by the release of nitric oxide or vasodilator prostaglandins such as PGE2 and PGI2. They also  cause the veins to contract due to direct stimulation of venous smooth muscle or from the release of PGF 2 alpha. Autacoids such as bradykinin is an effective 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?

The natriuretic peptides result in vasodilation furthermore natriuresis is effective for the treatment of congestive heart failure.

Drugs that combine neprilysin inhibition with ACE inhibition reduce the blood pressure in hypertensive patients and improve cardiac function in heart failure patients. LCZ696 has a beneficial effect in the treatment of patients with heart failure. It has shown to also lower blood pressure in hypertensive patients. As it increases plasmas ANP, increases cGMP levels, increase plasmas renin and ANG II levels.

What is neprilysin and what is the rationale for inhibiting its action in the treatment of heart failure?

the primary rationale for neprilysin inhibitor therapy in cardiovascular disease was to increase endogenous natriuretic peptide levels thus achieving vasodilatation and natriuresis.

Give examples of endothelium-derived vasodilators and vasoconstrictors.

Vasoconstrictors: receptor subtypes ETA and ETB, ET 1

Vasodilators: PGI2, Nitric oxide