Question 1: What do you understand by the term "endothelium-dependent" vasodilation? Explain

Endothelium-dependent vasodilators like bradykinin increase the intracellular calcium levels in the endothelium. This therefore leads to the synthesis of NO (an EDRF) in the endothelium. NO them makes its way to the vascular smooth muscle to cause a vaso-relaxing effect.

Question 2: When we talk about 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. 

On the other hand, 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". The effects are small.

Question 3: Explain how NO contributes to fatal pathology of septic shock

It is a systemic inflammatory response which is caused by an infection. Some components which are present in bacteria (endotoxins, cytokines and tumor necrosis) cause the formation of iNOS in macrophages, smooth muscle cells etc. formation of NO in a large area therefore leads to severe hypertension, shock and may also lead to death. 

Question 4: Which autacoids mechanism of action depends on effects on the guanylyl cyclase-cGMP system

Nitric oxide (NO)

Question 5: NO may be toxic to the cell. Which mechanisms are available to the body to counter this detrimental effect of NO?

our bodies release NOS enzyme inhibitors that competitively bind to the binding site of arginine  in NOS. Thus, arginine is not converted to nitric oxide. 

Question 6: 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. the function of TH1 which synthesizes NO. This is a 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.

Question 7: In which possible neurological and psychiatric disease is NO involved?

Parkinson's disease, stroke and amyotrophic lateral sclerosis, which result because of over stimulation of NMDA receptors and therefore causing an increase in the synthesis of NO which inevitably causes excitotoxic neuronal death.