Vascular Endothilium

Question 1

name the two groups of endothelial derived mediators

Answer 1

• EDRFS (eg, Nitric Acid, EDHFS- endothelial derived hyperpolarising factors)
• EDCFS (EG. endothelins, Thromboxane A2

Question 2

what is endothelin?

Answer 2

A potent and long-acting vasoconstrictor peptide

Three isoforms: ET-1, -2, -3

Question 3

what is endothelin stimulated and inhibited by?

Answer 3

stimulated by- endotoxin, cytokines, growth factors (GF), Adrenaline, hypoxia, low shear stress

Question 4

what does endothelin bind to?

Answer 4

Endothelin binds to two receptors ETA and ETB
 G-protein coupled
 ETA Expressed on vsmc  vasoconstriction
 ETA –receptor antagonist used in treating pulmonary
hypertension

Question 5

what is nitric acid and what effect does an imbalance of nitric acid have?

Answer 5

transmitter in CNS and PNS
produced widely in the body
impaired production associated with hypertension

Question 6

What role does NO play in immune function?

Answer 6

Inhibit platelet adhesion and aggregation
 Inhibit monocyte adhesion and migration
 Inhibit smc and fibroblast proliferation
 (Host defence: Contributes to cytotoxic killing
mechanisms of immune cells)

Question 7

What role does NO play in vascular function?

Answer 7

Induces smc relaxation via activaton of cGMP

dependent protein kinases in smc

Question 8

describe the synthesis and breakdown of NO

Answer 8

Synthesised by the oxidation of L-Arginine
 causes production of L-citruline + NO
 Nitric oxide synthases: 3 isoforms
-eNOS
-nNOS
-iNOS
 Basal production of NO
 NO is short acting
 Oxidised to nitrite/nitrate
 Forms nitrosothiols – release NO over a longer time period

Question 9

Hows does NO effect SMC?

Answer 9

-NO binds to soluble guanylate cyclase in smc leading to
activation of cGMP
-cGMP activates cGMP-dependent
protein kinases
-leads to Ca sequestration and reduced intracellular Ca
- causes SMC relaxation

Question 10

what substarte analogues inhibit the action of NO on SMC?

Answer 10

L-NMMA

L-NAME

Question 11

What drugs are used to counter underproduction of NO?

Answer 11

-Group of nitric acid donors
-Glyceryl trinitrate is a nitrovasodilator that acts by generating NO.
SNP (sodium nitroprusside)

Question 12

when are NO inhibitors used in drug therapy?

Answer 12

Used in NO overproduction eg. inflammation,

neurodegenerative diseases

Question 13

what can cause impaired NO production?

Answer 13

Reduced substrate levels
 Reduced activity of eNOS
 Reduced availability of NO
 Eg. quenching by superoxide anions

Question 14

what can be used in the potenation (increased strength) of NO?

Answer 14

Dietary suplementation of L-arginine
 Selective NO donors
 Antioxidants
 Beta adrenoceptor agonists that activate the L-arg/NO
pathway