Renate Coetzee

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Blog #2.4

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

Endothelium-dependent vasodilation is the concept that the endothelium controls vascular tone in a paracrine fashion (i.e., by secreting diffusible soluble mediators able to act on physically contiguous cells in order to induce vasodilation of vessels such as endothelium derived relaxing factor (EDRF).

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 always present in the organism in constant amounts regardless of its metabolic state. In the NOS system that is nNOS (neuronal) and eNOS (endothelium). Inducible enzymes are thus enzymes that are induced in the body during certain metabolic states. In the NOS system that is iNOS (inducible).

These enzymes act during different metabolic states to exert their effect in the body (i.e. to casue vasodilation of the body by synthesising nitric oxide).

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

Endotoxins from the bacterial wall induce the synthesis of iNOS in macrophages, neutrophils, T cells, hepatocytes, smooth muscle, endothelial cells and fibroblasts. This widespread synthesis of nitric oxide results in exaggerated hypotension, shock and in certain cases death. This can be reduced or reversed by means of NOS inhibitors in humans.

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?

The use of nitric oxide inhibitors can counter the toxic effects of NO on the body.

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

NO can have pro-inflammatory effects by recruiting certain leukocytes and releasing inflammatory mediators. This increases iNOS activity. The NO produced acts as an microbicide (advantage) and plays important role in the body via immune cell function.

NO can however exacerbate tissue injury if released for a prolonged time in the body (disadvantage). May then contribute to disease pathogenesis.

In which possible neurological and psychiatric diseases is NO involved?

Parkinson disease.