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BONTLE LETHETSA

Portfolio for Study Section 2.4

3 Oct 2021, 17:27 Publicly Viewable

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

“Endothelium-dependent” vasodilation explains that the endothelium controls vasodilation. Endothelium-dependent vasodilation is stimulated by increased blood flow, this is done by increasing shear stress on the endothelium.

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” enzyme	“Inducible” enzyme
Definition	Enzymes produced independently of the composition of a medium. Regarded as “housekeeping” enzymes Always present/expressed. E.g., Glucose metabolizing enzyme and COX-1 is also an example of a constitutive enzyme.	Enzymes produced when needed, only in the presence of enzymes. Also known as the “adaptive” enzyme. Used for the breaking-down of things in the cell. E.g., Lactose metabolizing enzyme and COX-2.
Pathological implications	Constitutive enzymes are produced at constant levels regardless of extent of demand.	Pathological implications affect synthesis of inducible enzymes. For instance, COX-2 is rapidly induced upon activation by inflammatory mediators, nitrogen, and hormones. Lactose metabolizing enzyme made only if lactose is the only available source of carbon. (Therefore, it is not produced if glucose is present-thus COX-2 is not produced during diabetes).
Physiological implications	Constitutive enzymes are synthesized at relatively constant levels regardless of physiological implications. This is because they play an essential role in maintaining cell processes or/and structure of cell.	Physiological implications change with ageing. Therefore, synthesis of inducible enzymes changes with age. For instance, the incidence of diabetes increases with age until about age 65 years, after which eventually both incidence and prevalence seem to level off, thus synthesis of COX-2 decreases during increased incidence of diabetes.

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

Septic shock occurs when infectious microorganisms in the bloodstream induce a profound inflammatory response causing hemodynamic decompensation.

Endotoxin components from the bacterial wall along with endogenously generated tumour necrosis factor (TNF)-α and other cytokines induce synthesis of iNOS in macrophages, neutrophils, and T cells, as well as hepatocytes, smooth muscle cells, endothelial cells, and fibroblasts. This widespread generation

of NO results in exaggerated hypotension, shock, and, in some cases, death.

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

Nitric oxide. Nitric oxide activated the conversion of guanylyl cyclase to activated guanylyl cyclase, this will eventually lead to the conversion of GTP to cGMP. The elevation of cGMP will lead to vasodilation and relaxation of smooth muscle.

If inhaled, NO leads to increased blood flow to parts of the lung exposed to NO and decreased pulmonary vascular resistance.

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

Arginase is an enzyme in the urea cycle that hydrolyses L-arginine to urea and L-ornithine. It suppresses nitric oxide production through numerous mechanisms.

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

NO plays an essential role in protecting the body via immune cell function. When there is an invasion of foreign antigens. During an inflammatory response, Th1 cells respond by synthesizing NO, which has effects on activity of Th1 cells.

NO stimulates the synthesis of inflammatory prostaglandins by activating cyclooxygenase isoenzyme 2 (COX-2). Through its effects on COX-2, its direct vasodilatory effects, and other mechanisms, NO generated during inflammation contributes to the erythema, vascular permeability, and subsequent oedema associated with acute inflammation.

In which possible neurological and psychiatric diseases is NO involved?

NO is involved in physiological functions such as noradrenaline and dopamine releases, memory and learning and certain pathologies such as schizophrenia, bipolar disorder, and major depression.