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CR2 > Nitric Oxide In The Vascular System > Flashcards

Nitric Oxide In The Vascular System Flashcards

1
Q

Is NO lipophilic or hydrophilic

A

Lipophilic

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2
Q

Is NO a free radical

A

Yes

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3
Q

How reactive is NO

A

Stable and unreactive

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4
Q

How and where is dietary nitrate converted to NO

A

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

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5
Q

Dietary sources of nitrate

A

Green leafy veg - lettuce, spinach, beetroot

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6
Q

Sources of NO

A

Diet
Endothelium
Nerves
Muscle
RBC

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7
Q

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

A

Endogenous NO

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8
Q

Which Enzyme is involved in endogenous NO formation

A

Nitric oxide synthase

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9
Q

3 main forms of nitrogen oxide synthase

A

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

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10
Q

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

A

Calcium

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11
Q

What type of enzyme is nitrogen oxide synthase

A

Oxidoreductase homodimer enzyme

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12
Q

What 3 domains are in each monomer of nitrogen oxide synthase

A

Reductase domain
Oxidase domain
Calmodulin domain

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13
Q

What happens to nitrogen oxide synthase when no BH4 is present

A

Destabilises, uncouples, and produces superoxide

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14
Q

How is nitric oxide synthesised

A

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

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15
Q

What conditions are needed for nitric oxide synthesis

A

NOS
oxygen

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16
Q

Which molecule is endogenous NO synthesised from

A

L arginine

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17
Q

Where is endothelial nitric oxide synthase found

A

Plasma membrane bound on Endothelium of blood vessels

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18
Q

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

A

Shear stress causing wall stretching

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19
Q

How does increased shear stress activate eNOS

A

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

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20
Q

Agonists which stimulate NO formation

A

ACh
Bradykinin
Substance P
Adenosine

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21
Q

Where is neuronal NOS found

A

Brain autonomic nitrergic nerves
Brain neurones
Skeletal muscle sarcolemma

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22
Q

What molecule is nNOS attached to on the muscle sarcollema

A

Dystrophin

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23
Q

How does NO cause vasodilation

A

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

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24
Q

What molecule does NO activate

A

Guanylate cyclase

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25
Q

How does NO maintain basal vascular tone

A

Continuous release from endothelium causes tonic vasodilation

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26
Q

How does NO maintain blood pressure

A

Reduced NO causes increased peripheral resistance increasing blood pressure

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27
Q

Does NO increase or decrease blood pressure

A

Decrease

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28
Q

What changes occur in the alerting/defence response

A

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

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29
Q

What change does NO mediate in the alerting/defence response

A

Forearm skeletal vasodilation

30
Q

What is the role of NO in exercising muscles

A

Vasodilation

31
Q

Which 2 molecules cause vasodilation in exercising muscles

A

NO
Adenosine

32
Q

What must NO overcome to cause vasodilation in exercising muscle

A

General vasoconstriction of arterioles in muscle caused by sympathetic nervous system

33
Q

What triggers NO formation in exercising muscle

34
Q

How is NO effected in dystrophic muscle

A

Less nNOS produced

35
Q

Why is less NO produced in dystrophic muscle

A

No dystrophin

36
Q

What are the effects of decr NO production in dystrophic muscle

A

Unrestrained sympathetic vasoconstriction
Transient functional muscle ischaemia

37
Q

Why is NOS activity inhibited during anaerobic exercise

A

NOS is oxygen dependent

38
Q

Which pathway generates NO in hypoxic conditions

A

Nitrate nitrite NO reductive pathways

39
Q

What enzyme is used in the nitrate nitrite NO reductive pathway

A

Xanthine oxidoreductase

40
Q

What conditions increase Xanthine oxidoreductase activity

A

Exercise induced lactic acid accumulation
Hypoxia

41
Q

Where is nitrate sourced for the nitrate nitrite NO reductive pathway

A

Muscle nitrate reservoir

42
Q

What is formed when NO reacts with oxyhaemoglobin

A

Nitrosylhaemoglobin

43
Q

How does NO increase delivery of O2 to hypoxic tissues

A

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

44
Q

How does NO increase coronary circulation during exercise

A

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

45
Q

What is glycerol trinitrate used to treat

46
Q

How is glycerol trinitrate administered

A

Sublingually

47
Q

What type of drug is GTN

A

Coronary vasodilator

48
Q

How does GTN work

A

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

49
Q

What stimulates the production of NO immediately after birth

A

First breath stimulates eNOS through oxygenation and shear stress

50
Q

What mediates pulmonary vasodilation immediately after birth

A

Pulmonary endothelial NO

51
Q

What upregulates expression of eNOS and PKG after birth

A

Increased oxygen tension

52
Q

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

A

Decreases pulmonary vascular resistance

53
Q

Persistent pulmonary hypertension of the newborn

A

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

54
Q

What causes persistent pulmonary hypertension of the newborn

A

Too little NOS or inhaled meconium prevents inhaled O2 reaching NOS

55
Q

How does NO contribute to erection

A

Promotes vasodilation and blood flow

56
Q

Which muscle does NO cause relaxation in to cause erection

A

Cavernosal smooth muscle

57
Q

Which neurotransmitters cause penile erection

58
Q

What causes erectile dysfunction

A

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

59
Q

How does Sildenafil(viagra) work

A

Ohosphodiesterase inhibitor - prevents cGMP breakdown enhancing NO mediates vasodilation

60
Q

How does NO exert an anti thrombotic action

A

Inhibits platelet adhesion and aggregation

61
Q

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

A

Intravascular clots

62
Q

Why can slow or stagnant blood flow cause clots

A

Less NO released

63
Q

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

64
Q

Endothelial dysfunction

A

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

65
Q

What does the endothelium become in endothelium dysfunction

A

Prothrombotic
Pro inflammatory

66
Q

Causes of endothelial dysfunction

A

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

67
Q

What can cause deficient NO production in the endothelium

A

Reduced L arginine bioavailability
Asymmetric dimethyl L arginine
Altered NOS

68
Q

What consumptive processes can turn NO into other species

A

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

69
Q

What can cause uncoupling of NOS

A

BH4 insufficiency

70
Q

What does asymmetric dimethyl L arginine do

A

Inhibits NO production

CR2 (33 decks)

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