Trigger 4: Best understanding

Question 1

humans endogenously produce 1mM of NO via

Answer 1

L-arginine pathway everyday

Question 2

what catalyses L-arginine pathway

Answer 2

NOS

Question 3

three types of NOS

Answer 3

eNOS
nNOS
iNOS

Question 4

eNOS found in

Answer 4

vascular endothelium

Question 5

when is eNOS activated

Answer 5

• in response to changes in blood velocity (shear stress0

- Ach, bradykinin, histamine etc

Question 6

eNOS controls

Answer 6

BP homeostasis by causing relaxation of smooth muscle

Question 7

NO activates

Answer 7

guanylate cyclase- which activates cGMP

Question 8

eNOS is

Answer 8

constitutive

Question 9

nNOS is expressed on

Answer 9

CNS and PNS tissue

Question 10

nNOS produces Now which acts as a

Answer 10

NT in nerves

Question 11

NO based neurotransmission may be

Answer 11

involved in matching cerebral blood flow with neural activity and memory

Question 12

nNOS is

Answer 12

constitutive

Question 13

iNOS is produced in

Answer 13

response to inflammation- aiding host defences to infection

Question 14

iNOS promotes

Answer 14

vasodilation associated with inflammation

Question 15

NO2 and NO3 are

Answer 15

storage pools for NO and really excreted

Question 16

NO donors are used for their

Answer 16

dilatory effect

Question 17

NO donors used to treat

Answer 17

angina and heart failure

Question 18

direct NO donors

Answer 18

release NO spontaneously

Question 19

indirect NO donors

Answer 19

require an enzyme or chemical reaction to release NO

Question 20

give an example of an direct NO donor

Answer 20

sodium nitroprusside

Question 21

negative of sodium nitroprusside

Answer 21

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

Question 22

indirect NO donors are all

Answer 22

organic

Question 23

negative of organic NO door

Answer 23

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

Question 24

give an example of a commonly used indirect nitrate donor

Answer 24

glyceryl trinitrate (GTN) and isosorbide mononitrate

Question 25

GTN and isosorbide mononitrate are

Answer 25

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

Question 26

all indirect NO donors require

Answer 26

present elf thiol groups to release NO at the tissue level

Question 27

why are indirect NO donor more potent

Answer 27

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

Question 28

what is thought o lad to nitrate tolerance

Answer 28

thiol depletion

Question 29

what is suggested to reduced nitrate tolerance

Answer 29

nitrate free intervals

Question 30

NOS activators

Answer 30

acetylcholine, bradykinin and adenosine

Question 31

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

Answer 31

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

Question 32

L-arignine pathway requires

Answer 32

oxygen

Question 33

alternative NOS-indpenedent mechanism of NO synthesis

Answer 33

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

Question 34

NO3 and NO2 are thought to act as

Answer 34

NO stores

Question 35

alternative mechanism of NO synthesis may be important for

Answer 35

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

Question 36

oxygen is rapidly depleted during

Answer 36

ischaemia

Question 37

reduction of NO3 to NO2 requires

Answer 37

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

Question 38

reduction of NO2 to NO requires (4)

Answer 38

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

Question 39

deoxygenated Hb has

Answer 39

reductase activity - conversion of nitrite to NO

Question 40

xanthine oxidoreductase, under hypoxic conditions, catalyses the

Answer 40

reduction of NO2 to NO

Question 41

thought that xanthine oxidoreducatse acts a

Answer 41

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

Question 42

XOR activity is

Answer 42

unregulated during hypoxia

Question 43

how is NO thought to protect the heart

Answer 43

protects against IR damage

Question 44

s-nitrothiol

Answer 44

No storage POOL

Question 45

what is considered the largest storage pool of NO

Answer 45

Nittites

Question 46

nitrite to NO mechanism

Answer 46

low phH (stomach low pO2 Deoxygenated Hn

Question 47

deoxyhaemoglobin

Answer 47

Hb without oxygen (blue)

Question 48

hypoxia causes

Answer 48

NOS inhibition- leads to reliant on NO2-NO pathway

Question 49

Loss of NO bioactivity contributes to ....

Answer 49

a variety of diseases

Question 50

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

Answer 50

inactivate it

Question 51

Hb scavenges

Answer 51

NO rapidly

Question 52

Hb is thought to have what activity

Answer 52

nitrate reductase activity

Question 53

therefore Hb is useful in what conditions

Answer 53

hypoxic-when L-arignine pathway cant occur

Question 54

endothelial dysfunction can cause

Answer 54

ischaemia and atheroosclerosis

Question 55

endothelial dysfunction is characterised by

Answer 55

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

Question 56

mechanism of impaired NO bioavailability (5)

Answer 56

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

Question 57

INTRACELLULAR inhibitors OF eNOS

Answer 57

Caveolin-1

Question 58

CIRCULATORY NOS inhibitors

Answer 58

ADMA

Question 59

nitrates and cancer

Answer 59

no consistent evidence that nitrate increase risk of cancer

Question 60

blue babies caused by

Answer 60

- 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

Question 61

what causes blue skin

Answer 61

haemoglobinaemia

Question 62

what else causes blue skin

Answer 62

too much potassium nitrate -haemoglobinaemia

Question 63

NO protects against IR

Answer 63

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

Question 64

NO can increase efficiency of

Answer 64

exercise and endurance- reducing O2 cost for a given workload

Question 65

NO protects against

Answer 65

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