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

The concept that the endothelium controls vascular tone in a paracrine fashion  was extremely innovative and relevant to vascular physiology. Numerous endothelium-dependent vasodilators, such as acetylcholine and bradykinin, act by increasing intracellular calcium levels in endothelial cells, leading to the synthesis of NO. NO diffuses to vascular smooth muscle, leading to vasorelaxation.

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

They are enzymes that are repeatedly being synthesized irrespective of physiological need. They have a greater physiological and pathological importance because they are always present in one are. 

Induced enzymes are enzymes which emerge after a particular substance has been added. This implies that the enzyme is in fact present before a substance, therefore the body has to excrete a substance before the enzyme "works". it has small effects.

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

This physiological production of NO is important for blood pressure regulation and blood flow distribution. Several lines of evidence suggest that a hyperproduction of NO by the inducible form of NO synthase (iNOS) may contribute to the hypotension, cardiodepression and vascular hyporeactivity in septic shock.

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

Nitric oxide (NO)

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

NOS enzyme inhibitors is release by our body, that competitively bind to the binding site of arginine  in NOS. (arginine is not converted to nitric oxide)

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

when you body reacts to infection or even injury it leads to the activation of leukocytes and release of inflammatory mediators. This causes an increase in iNOS levels in leukocytes. The NO produced is an important microbial agent. NO is  synthesized (good protective response). The vasodilator effects of NO and effects of COX2 carry a huge role in inflammation, it causes red skin, it increases vascular permeability and increases edema in acute conditions. The disadvantage of NO however would be, in both acute and chronic inflammation the excess NO production may cause tissue damage, psoriasis lesions, airway epithelium in asthma patients and inflammatory bowel lesions.

In which possible neurological and psychiatric diseases is NO involved? 

Parkinson's disease

stroke

amyotrophic lateral sclerosis