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

• Endothelium-dependent vasodilators  increase the intracellular calsium levels in the endothelium. Endothelium cells respond to vasorelaxants by releasing soluble EDRF. EDRF acts on vascular muscle to cause relaxation and gives a vaso-relaxing effect.
•  An increase in blood flow stimulates endothelium-dependent vasodilation by increasing shear stress on the endothelium, both in conduit and resistance vessels

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

• eNOS and nNOS are expressed constitutively and NO synthesis is relied on calcium regulation. Whereas iNOS is expressed through transcriptional induction when it is exposed to inflammatory mediators therefore NO synthesis is not regulated by calcium.

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

• Sepsis is a systemic inflammatory response that is caused by infection. Some components which are present in bacteria (endotoxins, cytokines and tumor necrosis) cause the formation of iNOS in macrophages, T-cells, hepatocytes . This formation of NO leads to shock, severe hypertension and possible death. 

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

• NO

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

• Intracellular glutathione protecting mechanisms against tissue damage caused by scavenging peroxynitrite. Peroxynitrite causes tissue damage during inflammation.

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

• NO activates COX-2 and causes the synthesis of inflammatory prostaglandins. Prostaglandins have vasodilatory effects and together with NO  can increase vascular permeability and lead to perivascular edema. Excessive NO can cause tissue injury.

In which possible neurological and psychiatric diseases is NO involved? 

• Parkinson's disease, stroke and amyotrophic lateral sclerosis.