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

Endothelium is responsible for vasodilation.

When blood flow increases it stimulates endothelium-dependent vasodilation by increasing shear stress on the endothelium, both in conduit and resistance vessels.

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?

Constitutive enzymes are ever present, they are produced at constant rates no matter the demand and are also constantly synthesized regardless of physiological or pathological implications.

Inducible enzymes are only produced when there is a need for them and that is in the presence of other enzymes Pathological or physiological implications can affect the synthesis of these enzymes.

iNOS is not regulated by , but after synthesis it is constitutively active.

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

Systemic shock is a systemic inflammatory response that is caused by infection. Endotoxins from the bacterial cell wall, TNf-α as well as other cytokines, induce the formation of iNOS to NO. Excessive increase in NO may lead to hypotension, shock or in some cases even death.

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?

The body releases NOS enzyme inhibitors and it will compete with NOS for the binding site of arginine thus preventing arginine from being converted NO.

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

NO plays a role in the body via immune cell function. When foreign antigens enter the body Th1 cells synthesizes NO and NO stimulates the inflammatory prostaglandins by activating COX 2. The inflammatory response of releasing NO can lead to erythema, vascular permeability and subsequent edema along with acute inflammation. Prolonged or excessive NO production can aggregate tissue injury. This can lead to psoriasis lesions, airway epithelium in asthma and inflammatory bowel lesions iNOS induction may also lead to disease pathogen

7. In which possible neurological and psychiatric diseases is NO involved?

• Parkinson's disease
• Amyotrophic lateral sclerosis
• Stroke