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(1-5) Translational Medical Science > Trigger 4: Best understanding > Flashcards

Trigger 4: Best understanding Flashcards

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Biology 101 flashcards USMLE® Step 1 flashcards
1
Q

humans endogenously produce 1mM of NO via

A

L-arginine pathway everyday

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2
Q

what catalyses L-arginine pathway

A

NOS

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3
Q

three types of NOS

A

eNOS
nNOS
iNOS

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4
Q

eNOS found in

A

vascular endothelium

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5
Q

when is eNOS activated

A
  • in response to changes in blood velocity (shear stress0

- Ach, bradykinin, histamine etc

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6
Q

eNOS controls

A

BP homeostasis by causing relaxation of smooth muscle

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7
Q

NO activates

A

guanylate cyclase- which activates cGMP

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8
Q

eNOS is

A

constitutive

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9
Q

nNOS is expressed on

A

CNS and PNS tissue

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10
Q

nNOS produces Now which acts as a

A

NT in nerves

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11
Q

NO based neurotransmission may be

A

involved in matching cerebral blood flow with neural activity and memory

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12
Q

nNOS is

A

constitutive

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13
Q

iNOS is produced in

A

response to inflammation- aiding host defences to infection

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14
Q

iNOS promotes

A

vasodilation associated with inflammation

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15
Q

NO2 and NO3 are

A

storage pools for NO and really excreted

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16
Q

NO donors are used for their

A

dilatory effect

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17
Q

NO donors used to treat

A

angina and heart failure

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18
Q

direct NO donors

A

release NO spontaneously

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19
Q

indirect NO donors

A

require an enzyme or chemical reaction to release NO

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20
Q

give an example of an direct NO donor

A

sodium nitroprusside

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21
Q

negative of sodium nitroprusside

A
  • drug contains cyanide- too much could potentially cause cynide poisoning
  • can worsen ventilation
  • can induce spontaneous tachycardia limiting hypotensive effects (requires B blocker)
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22
Q

indirect NO donors are all

A

organic

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23
Q

negative of organic NO door

A
  • extensive first pass metabolism
  • limited by development of tolerance
  • endothelial dysfunction
  • v.variable bioavailability
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24
Q

give an example of a commonly used indirect nitrate donor

A

glyceryl trinitrate (GTN) and isosorbide mononitrate

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25
Q

GTN and isosorbide mononitrate are

A

vasodilatory- relieving angina, heart failure and can be used as an anaesthesia

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26
Q

all indirect NO donors require

A

present elf thiol groups to release NO at the tissue level

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27
Q

why are indirect NO donor more potent

A

due to venous myocytes having more thiol groups- more available- more potent

28
Q

what is thought o lad to nitrate tolerance

A

thiol depletion

29
Q

what is suggested to reduced nitrate tolerance

A

nitrate free intervals

30
Q

NOS activators

A

acetylcholine, bradykinin and adenosine

31
Q

initially it was though that …….. was the primary source of NO for biological tissue

A

metabolism of L-arginine in oxygen rich environment by NOS to L-citrulline

32
Q

L-arignine pathway requires

A

oxygen

33
Q

alternative NOS-indpenedent mechanism of NO synthesis

A

operates when conventional NO production is impaired e.g. due to hypoxia (schema)

34
Q

NO3 and NO2 are thought to act as

A

NO stores

35
Q

alternative mechanism of NO synthesis may be important for

A

ischaemic conditions due to generation of NO from L-arginine being dependent on oxygen

36
Q

oxygen is rapidly depleted during

A

ischaemia

37
Q

reduction of NO3 to NO2 requires

A

facultative anaerobic bacteria in mouth, due to nitrates being very innert

38
Q

reduction of NO2 to NO requires (4)

A

1) acidification (stomach)
2) bacterial nitrate reductases
3) enzyme catalysis (xanthin oxidoreductase)
4) deoxygenated Hb

39
Q

deoxygenated Hb has

A

reductase activity - conversion of nitrite to NO

40
Q

xanthine oxidoreductase, under hypoxic conditions, catalyses the

A

reduction of NO2 to NO

41
Q

thought that xanthine oxidoreducatse acts a

A

a salvage pathway to maintain level of NO in situations where cNOS activity is reduced e.g. hypoxia

42
Q

XOR activity is

A

unregulated during hypoxia

43
Q

how is NO thought to protect the heart

A

protects against IR damage

44
Q

s-nitrothiol

A

No storage POOL

45
Q

what is considered the largest storage pool of NO

A

Nittites

46
Q

nitrite to NO mechanism

A

low phH (stomach
low pO2
Deoxygenated Hn

47
Q

deoxyhaemoglobin

A

Hb without oxygen (blue)

48
Q

hypoxia causes

A

NOS inhibition- leads to reliant on NO2-NO pathway

49
Q

Loss of NO bioactivity contributes to ….

A

a variety of diseases

50
Q

in the past it was thought that Hb reacted with NO sole to

A

inactivate it

51
Q

Hb scavenges

A

NO rapidly

52
Q

Hb is thought to have what activity

A

nitrate reductase activity

53
Q

therefore Hb is useful in what conditions

A

hypoxic-when L-arignine pathway cant occur

54
Q

endothelial dysfunction can cause

A

ischaemia and atheroosclerosis

55
Q

endothelial dysfunction is characterised by

A

reduced bioavailability of endothelial derived NO- a central mechanistic feat of CAD

56
Q

mechanism of impaired NO bioavailability (5)

A

1) oxidative stress
2) Substrate cofactor availability
3) retention of altered Hb
4) Increased expression of INTRACELLULAR inhibitors OF eNOS
5) increased conc of CIRCULATORY NOS inhibitors

57
Q

INTRACELLULAR inhibitors OF eNOS

A

Caveolin-1

58
Q

CIRCULATORY NOS inhibitors

A

ADMA

59
Q

nitrates and cancer

A

no consistent evidence that nitrate increase risk of cancer

60
Q

blue babies caused by

A
  • babies who were fed with private water supply (agricultural)
  • water had high levels of nitrate from fertilisers
  • NO competes with oxygen to bind with Hb- causing haemoglobinaemia
61
Q

what causes blue skin

A

haemoglobinaemia

62
Q

what else causes blue skin

A

too much potassium nitrate -haemoglobinaemia

63
Q

NO protects against IR

A

1) heart attack/stroke
2) blocked blood vessel
3) blood reperfusio injury in hypoxic area
4) nitrite/nitrate decrease amount of dead tissue

64
Q

NO can increase efficiency of

A

exercise and endurance- reducing O2 cost for a given workload

65
Q

NO protects against

A

metabolic syndrome

  • eNOS knock-out mouse
  • if you give them nittier- overcomes missing NO

(1-5) Translational Medical Science (26 decks)

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