Nitric Oxide In The Vascular System

Question 1

Is NO lipophilic or hydrophilic

Answer 1

Lipophilic

Question 2

Is NO a free radical

Answer 2

Yes

Question 3

How reactive is NO

Answer 3

Stable and unreactive

Question 4

How and where is dietary nitrate converted to NO

Answer 4

Nitrate -> nitrite in mouth
Nitrite -> NO in hypoxic tissues

Question 5

Dietary sources of nitrate

Answer 5

Green leafy veg - lettuce, spinach, beetroot

Question 6

Sources of NO

Answer 6

Diet
Endothelium
Nerves
Muscle
RBC

Question 7

What subcategory of NO is derived from sources in and near the vasculature

Answer 7

Endogenous NO

Question 8

Which Enzyme is involved in endogenous NO formation

Answer 8

Nitric oxide synthase

Question 9

3 main forms of nitrogen oxide synthase

Answer 9

NOS type 1 - neuronal
NOS type 2
NOS type 3 - endothelial

Question 10

What cofactor is needed by nitrogen oxide synthase types 1 and 3

Answer 10

Calcium

Question 11

What type of enzyme is nitrogen oxide synthase

Answer 11

Oxidoreductase homodimer enzyme

Question 12

What 3 domains are in each monomer of nitrogen oxide synthase

Answer 12

Reductase domain
Oxidase domain
Calmodulin domain

Question 13

What happens to nitrogen oxide synthase when no BH4 is present

Answer 13

Destabilises, uncouples, and produces superoxide

Question 14

How is nitric oxide synthesised

Answer 14

L arginine oxidised to L citrullanine+ NO, catalysed by NOS

Question 15

What conditions are needed for nitric oxide synthesis

Answer 15

NOS
oxygen

Question 16

Which molecule is endogenous NO synthesised from

Answer 16

L arginine

Question 17

Where is endothelial nitric oxide synthase found

Answer 17

Plasma membrane bound on Endothelium of blood vessels

Question 18

What promotes the dissociation of eNOS from Cav-1 allowing it to be released into the cytoplasm and activated

Answer 18

Shear stress causing wall stretching

Question 19

How does increased shear stress activate eNOS

Answer 19

Increased intracellular calcium and phosphorylation of eNOS, release of endothelium dependent agonists

Question 20

Agonists which stimulate NO formation

Answer 20

ACh
Bradykinin
Substance P
Adenosine

Question 21

Where is neuronal NOS found

Answer 21

Brain autonomic nitrergic nerves
Brain neurones
Skeletal muscle sarcolemma

Question 22

What molecule is nNOS attached to on the muscle sarcollema

Answer 22

Dystrophin

Question 23

How does NO cause vasodilation

Answer 23

Diffuses into underlying smooth muscle -> activates guanylate cyclase -> converts guanosine triphosphate to cGMP -> cGMP acts through cGMP dependent protein kinases -> myosin inactivated -> inhibit contraction

Question 24

What molecule does NO activate

Answer 24

Guanylate cyclase

Question 25

How does NO maintain basal vascular tone

Answer 25

Continuous release from endothelium causes tonic vasodilation

Question 26

How does NO maintain blood pressure

Answer 26

Reduced NO causes increased peripheral resistance increasing blood pressure

Question 27

Does NO increase or decrease blood pressure

Answer 27

Decrease

Question 28

What changes occur in the alerting/defence response

Answer 28

Incr BP Incr HR Incr forarm muscle blood flow Decr skin blood flow Decr visceral blood flow

Question 29

What change does NO mediate in the alerting/defence response

Answer 29

Forearm skeletal vasodilation

Question 30

What is the role of NO in exercising muscles

Answer 30

Vasodilation

Question 31

Which 2 molecules cause vasodilation in exercising muscles

Answer 31

NO Adenosine

Question 32

What must NO overcome to cause vasodilation in exercising muscle

Answer 32

General vasoconstriction of arterioles in muscle caused by sympathetic nervous system

Question 33

What triggers NO formation in exercising muscle

Answer 33

Ca influx

Question 34

How is NO effected in dystrophic muscle

Answer 34

Less nNOS produced

Question 35

Why is less NO produced in dystrophic muscle

Answer 35

No dystrophin

Question 36

What are the effects of decr NO production in dystrophic muscle

Answer 36

Unrestrained sympathetic vasoconstriction Transient functional muscle ischaemia

Question 37

Why is NOS activity inhibited during anaerobic exercise

Answer 37

NOS is oxygen dependent

Question 38

Which pathway generates NO in hypoxic conditions

Answer 38

Nitrate nitrite NO reductive pathways

Question 39

What enzyme is used in the nitrate nitrite NO reductive pathway

Answer 39

Xanthine oxidoreductase

Question 40

What conditions increase Xanthine oxidoreductase activity

Answer 40

Exercise induced lactic acid accumulation Hypoxia

Question 41

Where is nitrate sourced for the nitrate nitrite NO reductive pathway

Answer 41

Muscle nitrate reservoir

Question 42

What is formed when NO reacts with oxyhaemoglobin

Answer 42

Nitrosylhaemoglobin

Question 43

How does NO increase delivery of O2 to hypoxic tissues

Answer 43

Binds to and displaces O2 from oxyhaemoglobin, increasing O2 entering tissues and forming nitrosylhaemoglobin

Question 44

How does NO increase coronary circulation during exercise

Answer 44

Incr myocardium vasodilation Opens arterioles that are closed when heart is at rest

Question 45

What is glycerol trinitrate used to treat

Answer 45

Angina MI

Question 46

How is glycerol trinitrate administered

Answer 46

Sublingually

Question 47

What type of drug is GTN

Answer 47

Coronary vasodilator

Question 48

How does GTN work

Answer 48

Converted to NO in venous blood -> carried to heart -> dilates coronary vessels

Question 49

What stimulates the production of NO immediately after birth

Answer 49

First breath stimulates eNOS through oxygenation and shear stress

Question 50

What mediates pulmonary vasodilation immediately after birth

Answer 50

Pulmonary endothelial NO

Question 51

What upregulates expression of eNOS and PKG after birth

Answer 51

Increased oxygen tension

Question 52

How does NO cause an increase in pulmonary blood flow at birth

Answer 52

Decreases pulmonary vascular resistance

Question 53

Persistent pulmonary hypertension of the newborn

Answer 53

Normal reduction in pulmonary vascular resistance following first breath does not occur and most of R ventricular output remains in foetal state - bypasses lungs

Question 54

What causes persistent pulmonary hypertension of the newborn

Answer 54

Too little NOS or inhaled meconium prevents inhaled O2 reaching NOS

Question 55

How does NO contribute to erection

Answer 55

Promotes vasodilation and blood flow

Question 56

Which muscle does NO cause relaxation in to cause erection

Answer 56

Cavernosal smooth muscle

Question 57

Which neurotransmitters cause penile erection

Answer 57

ACh NO

Question 58

What causes erectile dysfunction

Answer 58

Endothelial dysfunction causes smooth muscle cavernosal contraction or cGMP degraded by phosphodiesterases facilitating smooth muscle contraction

Question 59

How does Sildenafil(viagra) work

Answer 59

Ohosphodiesterase inhibitor - prevents cGMP breakdown enhancing NO mediates vasodilation

Question 60

How does NO exert an anti thrombotic action

Answer 60

Inhibits platelet adhesion and aggregation

Question 61

What can happen when less NO is on the endothelium of blood vessels

Answer 61

Intravascular clots

Question 62

Why can slow or stagnant blood flow cause clots

Answer 62

Less NO released

Question 63

Are platelet mediated thrombotic responses aided by increase or decrease in NO

Answer 63

Decrease

Question 64

Endothelial dysfunction

Answer 64

Pathological state of the endothelium characterised by a reduction in the bioavailability of vasodilators, inc NO, making the endothelium pro inflammatory and prothrombotic

Question 65

What does the endothelium become in endothelium dysfunction

Answer 65

Prothrombotic Pro inflammatory

Question 66

Causes of endothelial dysfunction

Answer 66

Consumptive processes converting NO to other species Deficient NO production Altered NOS

Question 67

What can cause deficient NO production in the endothelium

Answer 67

Reduced L arginine bioavailability Asymmetric dimethyl L arginine Altered NOS

Question 68

What consumptive processes can turn NO into other species

Answer 68

Reaction with ROS creating peroxynitrite Uncoupling of NOS causing superoxide anions to be created instead of NO

Question 69

What can cause uncoupling of NOS

Answer 69

BH4 insufficiency

Question 70

What does asymmetric dimethyl L arginine do

Answer 70

Inhibits NO production