Blog#2.4

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

Vasodilation caused by substances that induce vasodilation and comes from the endothelium Different stimuli that are found in endothelial cells causes Nitric Oxide synthesis which in turn 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.  

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 Nitric Oxide  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  due to its role in prostaglandin synthesis in the COX2 pathway, 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. 

In which possible neurological and psychiatric diseases is NO involved? 

Parkinson’s disease, stroke.