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Translational Medical Sciences > Nitrate-Nitrite-Nitric Oxide > Flashcards

Nitrate-Nitrite-Nitric Oxide Flashcards

1
Q

How much nitrate is generated by our body in a day

A

1mmol/day

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2
Q

What can act as a storage pool for nitric oxide

A

Nitrate and nitrite

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3
Q

What are the three isoforms of NOS

A
  • eNOS
  • iNOS
  • nNOS
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4
Q

Describe the entero-salivary circulation of dietary nitrate

A
  • Nitrate from diet is ingest
  • Most of it it rapidly and completely absorbed by the upper GI tract
  • About 25% is stored in salivary glands and secreted in the mouth
  • In the tongue, nitrate is reduced to nitrite by facultative anaerobes
  • Nitrite is swallowed and some of it undergoes acidic reduction in the stomach to form NO while the rest is absorbed
  • About 60% of ingested nitrate is lost to urine within 48 hours
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5
Q

Why is arginine relevant to the synthesis of nitric oxide?

A

NOS relies on arginine as the nitrogen donor

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6
Q

How does the body get arginine?

A
  • from diet

- synthesised endogenously from other amino acids

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7
Q

What lifestyle measures are usually recommended by GPs to improve BP and reduce the risk of CVD?

A
  • weight loss
  • low salt diet
  • exercise
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8
Q

What is the difference between organic and inorganic nitrate?

A

organic nitrate contains carbon

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9
Q

Why has beetroot been used to treat angina?

A

because it’s a natural source of inorganic nitrate

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10
Q

What is nitric oxide a key regulator of?

A

vascular tone

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11
Q

What can lead to diminished nitric oxide reduction?

A
  • hypertension
  • hyperlipidemia
  • type 2 diabetes
  • chronic kidney disease
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12
Q

How is inorganic nitrate found in nature?

A

as a salt with potassium or sodium

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13
Q

What is nNOS used for?

A

CNS signalling

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14
Q

What is iNOS used for?

A

it’s a damage free radical, produced by WBCs and a part of the immune response

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15
Q

How is nitrate converted to nitrite within the body?

A
  • through facultative anaerobes
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16
Q

What effect will using antibacterial mouthwash have on nitrate levels within the body?

A
  • will increase and be secreted through urine
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17
Q

What is xanthine oxidoreductase?

A

an enzyme that reduces nitrite into nitric oxide

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18
Q

How is nitric oxide produced

A
  • oxidation of L-arginine by NOS
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19
Q

What is the bioavailability of nitrate?

A

almost 100%

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20
Q

Can nitrite be reduced to nitric oxide by the stomach?

A

yes as it undergoes acid reduction in the stomach

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21
Q

What are the local effects of nitric oxide in the stomach?

A
  • keeps the mucus layer thick

- increases gastric blood flow

22
Q

What are the different routes of nitrite reduction into nitric oxide?

A
  • acid catalysed
  • xanthine oxidoreductase
  • deoxyhaemoglobin and other haem proteins
  • NOS
23
Q

When are the systems of nitrite reduction to nitric oxide of most benefit?

A

during hypoxia or acidosis

eg. during heart attack or stroke

24
Q

What effect does nitric oxide have on blood vessels?

A

relaxes them to stabilise blood flow

25
Q

What does nitric oxide synthesis rely on?

A

oxygen and arginine (nitrogen donor)

26
Q

When is deoxyhemoglobin more commonly found?

A

hypoxia

27
Q

Which are higher; arterial nitrate levels or venous nitrate levels?

A

arterial

28
Q

What is vitamin D important for?

A

bone and vascular health

29
Q

What is vitamin D associated with?

A

frailty and mortality

30
Q

What affect can UV have on the nitrate levels in the body?

A

UV light can liberate nitrates from stores in the skin

31
Q

What are nitrosothiols?

A

storage molecules that can give up NO in certain conditions

32
Q

What mechanisms can impair bioavailability?

A
  • oxidative stress
  • substrate/cofactor availability
  • retention by altered haemoglobin
  • increased expression of intracellular eNOS inhibitors
  • increased inhibitors of NOS
33
Q

What is the role of nitric oxide in vascular control

A
  • vasodilation

- reduces release of superoxide radicals

34
Q

What are the substrates and cofactors in nitric oxide synthesis?

A

arginine and oxygen

35
Q

How does altered haemoglobin retain nitric oxide?

A

Glycated haemoglobin retains more nitric oxide

36
Q

What effect does inorganic nitrate have on blood circulation?

A

vasodilation

37
Q

What can organic nitrates be used to treat?

A
  • angina
  • heart attack
  • heart failure
38
Q

Name some benefits of NO donor drugs

A
  • lower systematic BP
  • rapid onset
  • inhibit platelet aggregation
39
Q

Name some limitations of NO donor drugs

A
  • can lead to endothelial dysfunction
  • extensive first pass metabolism (so concentration is greatly reduced)
  • susceptible to developing tolerance (need a reset period)
  • very high variability
  • unsure of specific mechanism by which NO3 => NO2
40
Q

What are the roles that NO plays in vascular health

A
  • vasodilator
  • protects against IR injury
  • anti-thrombotic
  • anti-inflammatory
  • reduces BP
  • inhibits platelet aggregation
41
Q

what are defects in bioavailaibility and endogenous synthesis of NO linked to

A

metabolic and cardiovascular disease

42
Q

What can excess NO result in

A

free radical formation

43
Q

Describe the NO signalling pathway

A
  • endothelial cells in the lumen of the vasculature express eNOS
  • eNOS produces NO
  • NO diffuses from endothelial cells into the smooth muscle cells and activates sGC
  • sGC converts GTP into cGMP
  • cGMP binds to L-type Ca channels and leads to:
    • decreased Ca
    • decreased MLCK activation
    • smooth muscle relaxation
    • vasodilation
44
Q

Name the 2 major sources of nitrates in mammals

A
  • from diet

- endogenous synthesis of nitrates into NO

45
Q

Name a major source of dietary nitrates

A

green leafy vegetables and beetroot

46
Q

Name some benefits of inorganic nitrates

A
  • lowers BP
  • protects from reperfusion injury
  • enhances athletic performance due to improved oxygen efficiency because of improved mitochondrial function
  • protects against metabolic syndromes (mice without NO3 gained weight and developed arthiritis which was cured by nitrate supplementation)
47
Q

Name some harms of inorganic nitrates

A
  • has been linked to cancer (mice fed high doses of nitrates develop lymphoma)
  • can cause blue baby syndrome due to methemoglobinemia (adults have enzyme that converts Fe3+ back to Fe2+ while babies don’t)
48
Q

What is methemoglobinemia

A
  • a disorder caused by the conversion of haemoglobin to methhaemoglobin (which has decreased deficiency for oxygen)
49
Q

How do NO donor drugs work

A

stabilise NO radical until necessary

50
Q

Name some common organic nitrates used

A
  • Nitroglycerin (acute pain relief in angina)
  • ISMN (chronic pain relief in angina, slow release)
  • SNP (rapidly lower BP in hypertensive crisis, cyanide groups can be associated with cyanidosis)

Translational Medical Sciences (8 decks)

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