Trigger 4: Nitrite-nitric oxide systema introduction Flashcards

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1
Q

NO3-

A

nitrate

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2
Q

NO2-

A

nitrite

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3
Q

NO

A

nitric oxide

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4
Q

NOS

A

nitric oxide synthase

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5
Q

where do you get nitrates from

A
  • Diet

- oxidation of NO from L-arginine NOS pathway

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6
Q

foods high in nitrates

A

beetroot, turnips, spinach

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7
Q

outline the Nitrate, nitrite and nitric oxide cycle

A

1) Nitrate is gained from the diet
2) it is either excreted in the kidneys or reduced to Nitrite
3) Nitrite is further reduces to Nitric Oxide or producing using NOS

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8
Q

Nitric oxide is a key

A

regulator of vascular tone

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9
Q

what occurs when there is diminished production of NO

A

Hypertension

Hyperlipidaemia

Chronic kidney disease

T2DM

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10
Q

how much nitrate per day do we generate from - oxidation of nitric oxide from L-arginine NOS pathway

A

1mmol

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11
Q

how much nitrate eaten in typical western diet?

A

1-2mmol

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12
Q

how is nitrate made endogenously

A

oxidation of nitric oxide during L-arginine NOS pathway

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13
Q

nitrate and nitrite may act as

A

storage pools for NO

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14
Q

Nitric oxide synthase are

A

a family of enzymes catalyzing the production of nitric oxide (NO) from L-arginine.

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15
Q

how many isoforms of NOS

A

3

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16
Q

how many are constitutive

A

2

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17
Q

how many are inducible

A

1

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18
Q

which two types are constitutive (cNOS)

A

EndothelialNOS (eNOS)

NeuronalNOS (nNOS)

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19
Q

which type is inducible

A

inducibleNOS

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20
Q

nNOS and eNOS

A

synthesises NO in response to increased intracellular calcium levels

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21
Q

is dependent on iNOS

A

no it is independent of the level of calcium in the cell

22
Q

NOS and calmodulin

A

all of the NOS isoforms are dependent on the binding of calmodulin. Increases in cellular calcium lead to increases in levels of calmodulin and the increased binding of calmodulin to eNOS and nNOS leads to a transient increase in NO production by these enzymes.

23
Q

iNOS and calmodulin

A

iNOS is not dependent on calcium, due to it being bale to bind tightly to calmodulin even at very low cellular concentration of calcium
–> therefore iNOS activity doesn’t respond to changes in calcium levels in the cell

24
Q

which NOS maintain the basal NO

A

continuously produced by cNOS- activated by Ca2+ release

25
Q

how is calcium released?

A

sheering forces e.g. when blood pressure rises

26
Q

outline the cNOS pathway

A

1) increased blood flow caused by increased BP caused calcium to flow into the endothelial cell
2) calcium activates cNOS
3) cNOS converts L-arginine to NO
4) NO moves into neighbouring smooth muscle cells
5) NO binds to GC (guanylate cyclase) and activates it
5) GC activates GTP which is converted to cGMP
6) cGMP activates myosin light change phosphatase which causes relaxation of smooth muscle

27
Q

where are nNOS expressed

A

in neurones and regulates the release of catecholamines in the heat

28
Q

where are eNOS expressed

A

expressed by platelets, promotes diastolic relaxation and decreases oxygen consumption in cardiac muscle

29
Q

what enhances eNOS activity

A

Each, bradykinin, histamine and increased intracellular calcium

30
Q

Shear stress and hormones such as insulin and plasma albumin increase

A

eNOS-derived NO production independent of changes in intracellular Ca2+

31
Q

iNOS is only active during

A

infection and inflammation

32
Q

where are iNOS found

A

within macrophages- participating in the early immune defence response

33
Q

which type of NOS produces the most NO

A

iNOS

34
Q

which types of bacteria reduce nitrate (from food) in the mouth

A

facultative anaerobes found on the dorm of the tongue

35
Q

where is nitrate converted to nitrite

A

in the upper gastrointestinal tract

36
Q

some nitrite will undergo …. to NO in the stomach

A

acidic reduction

37
Q

what happens to the nitrite not converted to NO in the stomach

A

it is absorbed

38
Q

how much ingested nitrate is lost in the urine within 48h

A

60%

39
Q

mouthy and nitrite

A

using mouthwash can deplete nitrite stores in the mouth- by killing the nitrite producing bacteria

40
Q

why are facultative anaerobic bacteria require to convert nitrate to nitrite

A

due to nitrate being very INNERT

41
Q

NO is a key signalling molecule involved in

A

regulation of BP

42
Q

which pathways stimulate NOS ativity

A

1) the force of blood flow

2) Endothelial receptors are activated by certain ligand (receptor-stimualted NO formation)

43
Q

ligands for receptor-stimulated NO formation

A

Ach, bradykinin, substance-P and adenosine

44
Q

what do both these NOS stimulating pathways cause

A

increased Ca2+

45
Q

characteristic of NO

A
  • short half life
  • lots of it diffused into the bloodstream where it binds to Hb and breaks down
  • lots diffused out of endothelial cells into smooth muscle cellls
46
Q

how does cGMP cause smooth muscle relaxation

A

1) activate protein kinase G (PKG) which inhibits calcium channels, preventing smooth muscle contraction - decreased peripheral resistance, decreased BP
2) activates K+ channels- potassium efflux- hyperpolarisation= relaxation
3) stimulate cGMP-dependent protein kinase that activates MLCP- causing dephospho rylation and relaxation

47
Q

nitrite reduction to NO used

A
  • acid catalysis
  • xanthine oxidoreductase
  • Deoxyhaemoglobin and other haem proteins
  • Nitric oxide synthase
48
Q

what other effects does endothelial NO have

A
  • inhibits platelet aggregation- preventing formation of thrombi
  • anti-inflammatory
  • vasodilation - inhibiting angiotensin II and sympathetic NS innervation
49
Q

how does NO affect the heart

A

All three NOS are expressed in the heart.

  • increases in NOS= reduction of heart rate i.
50
Q

large amounts of NO have a

A

negative inotropic affect on the heart

51
Q

small amounts of NO have a

A

positive inotropic effect (increases contraction speed)