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

An increase in blood flow stimulates endothelium-dependent vasodilation by increasing shear stress on the endothelium, both in conduit and resistance vessels. Activation of ET-B1 receptors on the endothelium causes vasodilatation by inducing the release of NO and PGI2. In ED, ET-B1 receptors on the endothelial cells are downregulated, while ET-B2 receptors on smooth muscle cells are upregulated, thus enhancing vasoconstriction

• 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 adaptive enzyme or inducible enzyme is an enzyme that is expressed only under conditions in which it is clearly of adaptive value, as opposed to a constitutive enzyme which is produced all the time. The Inducible enzyme is used for the breaking-down of things in the cell. Constitutive enzymes are maintained at constant concentration, without regard to metabolic need or substrate concentration. Their role in maintaining cell processes or structure is critically important, so they are never “off.” Inducible enzymes are not maintained at a constant concentration but are induced to be manufactured only when substrate is available.

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

In human septic shock, inhibition of NO synthesis has been shown to alter hemodynamic variables. excessive production of NO leads to severe hypotension and may cause signs of shock.

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

Natriuretic peptide

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

Nitric oxide (NO) is a signaling molecule that plays a key role in the pathogenesis of inflammation. It gives an anti-inflammatory effect under normal physiological conditions. On the other hand, NO is considered as a pro-inflammatory mediator that induces inflammation due to over production in abnormal situations.

• In which possible neurological and psychiatric diseases is NO involved?

Autism, OCD