Trigger 4: Nitrite-nitric oxide systema introduction

Question 1

NO3-

Answer 1

nitrate

Question 2

NO2-

Answer 2

nitrite

Question 3

NO

Answer 3

nitric oxide

Question 4

NOS

Answer 4

nitric oxide synthase

Question 5

where do you get nitrates from

Answer 5

• Diet

- oxidation of NO from L-arginine NOS pathway

Question 6

foods high in nitrates

Answer 6

beetroot, turnips, spinach

Question 7

outline the Nitrate, nitrite and nitric oxide cycle

Answer 7

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

Question 8

Nitric oxide is a key

Answer 8

regulator of vascular tone

Question 9

what occurs when there is diminished production of NO

Answer 9

Hypertension

Hyperlipidaemia

Chronic kidney disease

T2DM

Question 10

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

Answer 10

1mmol

Question 11

how much nitrate eaten in typical western diet?

Answer 11

1-2mmol

Question 12

how is nitrate made endogenously

Answer 12

oxidation of nitric oxide during L-arginine NOS pathway

Question 13

nitrate and nitrite may act as

Answer 13

storage pools for NO

Question 14

Nitric oxide synthase are

Answer 14

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

Question 15

how many isoforms of NOS

Answer 15

3

Question 16

how many are constitutive

Answer 16

2

Question 17

how many are inducible

Answer 17

1

Question 18

which two types are constitutive (cNOS)

Answer 18

EndothelialNOS (eNOS)

NeuronalNOS (nNOS)

Question 19

which type is inducible

Answer 19

inducibleNOS

Question 20

nNOS and eNOS

Answer 20

synthesises NO in response to increased intracellular calcium levels

Question 21

is dependent on iNOS

Answer 21

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

Question 22

NOS and calmodulin

Answer 22

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.

Question 23

iNOS and calmodulin

Answer 23

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

Question 24

which NOS maintain the basal NO

Answer 24

continuously produced by cNOS- activated by Ca2+ release

Question 25

how is calcium released?

Answer 25

sheering forces e.g. when blood pressure rises

Question 26

outline the cNOS pathway

Answer 26

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

Question 27

where are nNOS expressed

Answer 27

in neurones and regulates the release of catecholamines in the heat

Question 28

where are eNOS expressed

Answer 28

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

Question 29

what enhances eNOS activity

Answer 29

Each, bradykinin, histamine and increased intracellular calcium

Question 30

Shear stress and hormones such as insulin and plasma albumin increase

Answer 30

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

Question 31

iNOS is only active during

Answer 31

infection and inflammation

Question 32

where are iNOS found

Answer 32

within macrophages- participating in the early immune defence response

Question 33

which type of NOS produces the most NO

Answer 33

iNOS

Question 34

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

Answer 34

facultative anaerobes found on the dorm of the tongue

Question 35

where is nitrate converted to nitrite

Answer 35

in the upper gastrointestinal tract

Question 36

some nitrite will undergo .... to NO in the stomach

Answer 36

acidic reduction

Question 37

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

Answer 37

it is absorbed

Question 38

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

Answer 38

60%

Question 39

mouthy and nitrite

Answer 39

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

Question 40

why are facultative anaerobic bacteria require to convert nitrate to nitrite

Answer 40

due to nitrate being very INNERT

Question 41

NO is a key signalling molecule involved in

Answer 41

regulation of BP

Question 42

which pathways stimulate NOS ativity

Answer 42

1) the force of blood flow | 2) Endothelial receptors are activated by certain ligand (receptor-stimualted NO formation)

Question 43

ligands for receptor-stimulated NO formation

Answer 43

Ach, bradykinin, substance-P and adenosine

Question 44

what do both these NOS stimulating pathways cause

Answer 44

increased Ca2+

Question 45

characteristic of NO

Answer 45

- 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

Question 46

how does cGMP cause smooth muscle relaxation

Answer 46

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

Question 47

nitrite reduction to NO used

Answer 47

- acid catalysis - xanthine oxidoreductase - Deoxyhaemoglobin and other haem proteins - Nitric oxide synthase

Question 48

what other effects does endothelial NO have

Answer 48

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

Question 49

how does NO affect the heart

Answer 49

All three NOS are expressed in the heart. - increases in NOS= reduction of heart rate i.

Question 50

large amounts of NO have a

Answer 50

negative inotropic affect on the heart

Question 51

small amounts of NO have a

Answer 51

positive inotropic effect (increases contraction speed)