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TMS exam > 4 - overview of nitrate-nitrite-nitric oxide system > Flashcards

4 - overview of nitrate-nitrite-nitric oxide system Flashcards

1
Q

high BP increases risk of which types of disease

A

cardiovascular

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2
Q

examples of reasons why people wouldn’t want to take medication

A

unnatural

unhealthy

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3
Q

lifestyle recommendations to decrease BP

A

eat less salt

increase exercise

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4
Q

why is beetroot juice recommended to lower blood pressure

A

source of inorganic nitrate

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5
Q

function of nitric oxide n cardiovascular system

A 
main regulator of vascular tone
lowers BP
relaxes vascular smooth muscles
dilates blood vessels
inhibits aggregation of platelets to prevent thrombosis
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6
Q

when do blood vessels reduce their nitric oxide production

A

during cv disease states

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7
Q

how is nitrate produced in the body

A

oxidation of nitric oxide from L-arginine NOS pathway

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8
Q

what is the by-product of nitric oxide oxidation

A

free radical

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9
Q

how much inorganic nitrate is consumed in the typical western diet per day

A

1-2 mmmol

mainly from green, leafy vegetables

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10
Q

what is NO2-

A

nitrite

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11
Q

what is the symbol for nitrate

A

NO3-

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12
Q

why is nitrite concentration higher in saliva than plasma

A

nitric oxide is concentrated in the salivary gland

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13
Q

how do you convert nitrate or nitrite back to nitric oxide

A

reduction reaction

they gain oxygen

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14
Q

where is nitrite reduced to nitric oxide in the body

A

catalysed by acidic environments e.g. the stomach

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15
Q

why is nitric oxide important in the stomach

A

increases gastric blood flow
increases mucosal covering
reacts with food
gets absorbed into the bloodstream

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16
Q

which enzymes catalyses reduction of nitrite to NO

A

xanthine oxidoreductase

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17
Q

which enzyme catalyses production of nitric oxide from L-arginine

A

nitric oxide synthase

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18
Q

why do blood vessels need nitric oxide

A

needed to keep blood vessels relaxed and keep blood flow going

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19
Q

how do strokes effect NO

A

they can prevent nitric oxide synthesis

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20
Q

S-Nitrosothiol

A

R-SNO
formed when nitrite interacts with other molecules (such as sulfur atom of a thiol) to products alternative products to NO

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21
Q

why does nitric oxide need to be stored in the body in other forms

A

nitric oxide is an unstable free radical
has a very short half life
rapidly oxidises to nitrite

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22
Q

why is nitric oxide known as a free radical

A

it contains unpaired electrons

23
Q

other bodily functions of nitric oxide

A

increases cerebral blood flow (oxygen to the brain)
important for penile erection
dilates blood vessels –> increases blood flow to the kidney
dilates pulmonary vessels

24
Q

role of NO in immunity

A

Modulates T cell-mediated immune response

25
Q

why might bioavailability of NO be impaired

A

oxidative stress –> over-production of free radicals

low co-factor availability (low arginine)

retention by altered haemaglobin –>glycated haemaglobin holds onto NO and doesnt release it correctly

26
Q

what are the 3 forms of nitric oxide synthase

A 
endothelial NOS (eNOS)
neuronal NOS (nNOS)
inducible NOS (iNOS)
27
Q

which NOS forms are constitutive

A

eNOS

nNOS

28
Q

which forms of NOS have steady levels in th body

A

nNOS

eNOS

29
Q

where are eNOS and nNOS found in the body?

A

endothelial cells, neurons, skeletal muscles, epithelial cells and many other tissues.

30
Q

how is iNOS induced?

A

by specific cytokines

often in response to inflammatory conditions

31
Q

product of nitrite oxidation with oxyhaemaglobin

A

nitrate

32
Q

product of nitric oxide directly reacting with oxyhaemaglobin

A

methhaemaglobin and nitrate

33
Q

most common nitrosylated product in plasma.

A

R-SNO

34
Q

why is production of S-nitrosothiols common

A

nitric oxide has a high affinity for sulfhydryl groups (thiols)

35
Q

what is the main storage form of nitric oxide

A

nitrate (most stable)

36
Q

role of caveolin-1

A

modulates NO production

37
Q

how is cGMP produced

A

when nitric oxide activates smooth muscle soluble guanylyl cyclase (GC)

38
Q

how does cGMP effect smooth muscles

A

Increased intracellular cGMP inhibits calcium entry into the cell
–> decreased intracellular calcium concentration

activation of myosin light chain kinase

both causes smooth muscle relaxation

39
Q

when is caveolin-1 concentration increased

A

in cv disease states

40
Q

which type of blood vessel does nitric oxide effect the most

A

affects veins more than arteries

80% of blood is found in veins so dilation of veins has bigger effect

41
Q

where is NO produced

A

vascular endothelium

42
Q

which types of NOS are calcium dependent

A 
constitutive NOS (cNOS) 
(eNOS and nNOS)
43
Q

2 mechanisms to stimulate NO production

A

flow-dependent formation
- increase in blood flow stimulates release of Ca2+ and activates cNOS

receptor-stimulated formation
- ligands bind to endothelial receptors stimulating Ca2+ release

44
Q

2nd messenger in vasodilation

A

cyclic GMP

  • inhibits Ca2+ entry/activates K+ channels –> hyperpolarisation
  • activates myosin light chain phosphotase
45
Q

definition of bioavailabilty

A

the rate at which molecules enter the systemic circulation and can therefore access the site of action

46
Q

mechanism of cav-1

A

intracellular eNOS inhibitor
binds to eNOS and prevents binding of Ca2+ or CM
anchors eNOS in the membrane
reduces its ability to generate NO

47
Q

bioavailability of orally ingested nitrates

A

almost 100%
absorbed in the upper GI tract rapidly
bypassed first-pass metabolism in the liver

48
Q

how does NOS contribute to oxidative stress in mitochondria

A

NO binds to COX enzyme (competes with oxygen)

results in partial inhibition of mitochondrial respiration

49
Q

effect of hypoxia

A

increased conversion of nitrite to nitric oxide (instead of nitrite to nitrate)
dilatory effect enhanced

50
Q

BH4

A

co-factor
involved with all 3 NOS isoforms
reduces the haem iron of the enzyme to ultimately form an iron-oxy species that hydroxylates L-arginine to produce NO

51
Q

effect of increased expression of intracellular inhibitors of eNOS (Caveolin-1)

A

reduces bioavailability of NO

52
Q

what % of ingested inorganic nitrates is excreted in urine

A

60%

53
Q

what is sGC

A

soluble Guanylyl-cyclase

54
Q

role of facultative anaerobes after inorganic nitrates have been ingested

A

reduce NO3- to NO2- on the surface of the tongue

before NO2- is swallowed

TMS exam (22 decks)

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