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

This means that the endothelium cells in vascular tissue relax (dilate) when exposed to vasorelaxants through the release of endothelial-derived relaxing factor (EDRF). This factor induces relaxation of the vascular muscle. Endothelium-dependant vasodilators include acetylcholine and bradykinin. These vasodilators increase the calcium concentration inside the cells which induces Nitric oxide synthesis. The NO then travels to the vascular smooth muscle leading causing vasorelaxation.

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

An inducible enzyme are enzymes that are only active/present when needed and is used to break down molecules whereas constitutive enzymes which are continually being produced

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

Sepsis is inflammation caused by infectivity. The increased synthesis of NO contributes to more intense hypertension, shock and rarely possible death. Hypertension can be reversed via NO synthesis inhibitors such as sGC inhibitor methylene blue.

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

Autacoids act as local hormones in the body. When NO diffuses into the smooth muscle it activated the synthesis of guanylyl cyclase cGMP. This product activated protein kinase G decreasing the inward flow of calcium into the cell. With calcium influx being reduced the muscle will cease to contract.

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

Regarding the damage caused by NO through chronic and acute inflammation, iNOS inhibitors can serve as a form of protection.

NOS inhibitors can also be used in therapy to decrease neuronal damage.

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

NO can stimulate the synthesis of inflammatory prostaglandins through the activation of COX-2, this then produces the desired vasodilation effect. NO has its advantages by contributing to increased vascular permeability and disadvantages where the prolonged effects of NO (inflammation) can cause tissue damage.

7. In which possible neurological and psychiatric diseases is NO involved? 

NO acts as an important neurotransmitter in the CNS. NO is synthesised at the post-synaptic cleft. When too much NO is synthesised it can cause excitotoxic neuronal death in neurological diseases such as amyotrophic lateral sclerosis a d Parkinson’s disease.