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

Vasodilation caused by substances that induce vasodilation and originate from the endothelium (also synthesised from endothelium. Different stimuli that are found in endothelial cells causes NO synthesis (ex: increased cellular calcium etc) NO causes vasodilation. Thus it can be an endothelium-dependent vasodilator. 

• 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 enzymes that are synthesised at a constant level. (Produced in constant amounts regardless of substrate concentration) 
Inducible enzymes are enzymes that is synthesised only when they add adaptive value-or when exposed to a substrate. 

Because constitutive enzymes are more constant-and therefore always present the chances of them being affected by pathology is higher than that of inducible enzymes that are temporary. 

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

Many substances (endotoxins, cytokines, TNF-alpha) that are released by sepsis lead to the synthesis of iNOS located in macrophages, smooth muscle etc. This can lead to excessive production of NO which can lead to severe hypotension and shock associated with sepsis. 

• Which autacoids’ mechanism of action depends on effects on the guanylyl cyclase-cGMP system?

Nitric Oxide 

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

Scavengers of superoxide anion such as superoxide dismutase may protect NO, enhancing its potency and prolonging its duration of action. Nitrate tolerance.

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

NO that is released not only causes vasodilation, but due to its role in prostaglandin synthesis in the COX2 pathway, it results in an inflammatory response. This contributes to erythema, vascular permeability and oedema associated with acute inflammation. 

Disadvantageous: Excessive secretion of NO can worsen tissue injury and have an influence on disease pathology. 

Advantageous: NO that is produced inflammation, along with peroxynitrite that forms from its interaction with superoxide, is an important microbicide. NO also appears to play an important protective role in the body via immune cell function.

• In which possible neurological and psychiatric diseases is NO involved? 

Parkinson’s disease, stroke.