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

Endothelium is responsible for vasodilation.

An increase in blood flow 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 always present and are produced at constant rates no matter the demand as well as constantly synthesized regardless of physiological and pathological implications.

Inducible enzymes are only produced when it is needed that is in the presence of other enzymes, pathological and physiological implications can affect the synthesis of the enzymes.

 iNOS is not regulated by calcium, but after synthesis is constitutively active. In macrophages and several other cell types, iNOS is normally not readily detectable until inflammatory mediators induce the transcription of the iNOS gene, resulting in accumulation of iNOS and synthesis of large quantities of NO.

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

It is a systemic inflammatory response caused by infection. Endotoxins from the bacterial cell wall, together with TNf-α and other cytokines, induce the synthesis of iNOS to NO. Excessive increase in NO leads to hypotension or shock or in some cases it can lead to 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 which compete with NOS for the binding site of arginine to prevent arginine from being converted Nitric oxide.

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

NO also appears to play an important protective role in the body via immune cell function. When challenged with foreign antigens, Th1 cells respond by synthesizing NO.

NO also stimulates the synthesis of inflammatory prostaglandins by activating COX-2. Through its effects on COX-2, its direct vasodilatory effects, and other mechanisms, NO generated during inflammation contributes to the erythema, vascular permeability, and subsequent edema associated with acute inflammation.

In both acute and chronic inflammatory conditions, prolonged or excessive NO production may exacerbate tissue injury. Psoriasis lesions, airway epithelium in asthma, and inflammatory bowel lesions in humans all demonstrate elevated levels of NO and iNOS, suggesting that persistent iNOS induction may contribute to disease pathogen.

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

• Parkinson's disease,
• Stroke
• Amyotrophic lateral sclerosis