NO And Atherosclerosis

Question 1

Describe the structure of a blood vessel.

Answer 1

Luminal surface lined by intima.
IEL
media =smooth muscle held together by collagen and elastic fibres (relax and contract)
EEL
Adventitia - outer loose matrix of elastin, smooth muscle, fibroblasts and collagen.
Capillaries lined by epithelial.

Question 2

What is the effect of a reduction in BH4 levels?

Answer 2

NO synthesis uncoupled from NADPH consumption –> abnormal electron flow and superoxide production.

Question 3

What results from O2.- and NO?

Answer 3

React 3-4 times faster than dismutation of O2.- by SOD to form ONOO-
At neutral pH ONOO- can become protonated to form peroxynitrous acid
Homolytic cleavage –> hydroxyl like NO2 radical.

Question 4

What is atherosclerosis?

Answer 4

Accumulation of cholesterol deposits in mphages in large and medium arteries –> proliferation of certain cell types within arterial wall –> impedes blood flow.

Question 5

How are modified LDLs pro inflammatory?

Answer 5

Stimulate expression of monocytes chemotactic protein 1 in endothelial cells.
Promote differentiation of monocytes into mphages

Induce macrophages to release cytokines stimulating adhesion molecule expression on endothelial cells.

Question 6

Why may exogenous nitrovasodilators work?

Answer 6

Release NO in close proximity to vascular smooth muscle - at site removed from O2 source so NO can interact with SMO guanylate cyclase before inactivation by superoxide.

Question 7

What are the benefits of HDL?

Answer 7

Inhibits LDL oxidation
Promotes cholesterol efflux
Inhibits adhesion molecule expression.