4 - overview of nitrate-nitrite-nitric oxide system

Question 1

high BP increases risk of which types of disease

Answer 1

cardiovascular

Question 2

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

Answer 2

unnatural

unhealthy

Question 3

lifestyle recommendations to decrease BP

Answer 3

eat less salt

increase exercise

Question 4

why is beetroot juice recommended to lower blood pressure

Answer 4

source of inorganic nitrate

Question 5

function of nitric oxide n cardiovascular system

Answer 5

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

Question 6

when do blood vessels reduce their nitric oxide production

Answer 6

during cv disease states

Question 7

how is nitrate produced in the body

Answer 7

oxidation of nitric oxide from L-arginine NOS pathway

Question 8

what is the by-product of nitric oxide oxidation

Answer 8

free radical

Question 9

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

Answer 9

1-2 mmmol

mainly from green, leafy vegetables

Question 10

what is NO2-

Answer 10

nitrite

Question 11

what is the symbol for nitrate

Answer 11

NO3-

Question 12

why is nitrite concentration higher in saliva than plasma

Answer 12

nitric oxide is concentrated in the salivary gland

Question 13

how do you convert nitrate or nitrite back to nitric oxide

Answer 13

reduction reaction

they gain oxygen

Question 14

where is nitrite reduced to nitric oxide in the body

Answer 14

catalysed by acidic environments e.g. the stomach

Question 15

why is nitric oxide important in the stomach

Answer 15

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

Question 16

which enzymes catalyses reduction of nitrite to NO

Answer 16

xanthine oxidoreductase

Question 17

which enzyme catalyses production of nitric oxide from L-arginine

Answer 17

nitric oxide synthase

Question 18

why do blood vessels need nitric oxide

Answer 18

needed to keep blood vessels relaxed and keep blood flow going

Question 19

how do strokes effect NO

Answer 19

they can prevent nitric oxide synthesis

Question 20

S-Nitrosothiol

Answer 20

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

Question 21

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

Answer 21

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

Question 22

why is nitric oxide known as a free radical

Answer 22

it contains unpaired electrons

Question 23

other bodily functions of nitric oxide

Answer 23

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

Question 24

role of NO in immunity

Answer 24

Modulates T cell-mediated immune response

Question 25

why might bioavailability of NO be impaired

Answer 25

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

Question 26

what are the 3 forms of nitric oxide synthase

Answer 26

``` endothelial NOS (eNOS) neuronal NOS (nNOS) inducible NOS (iNOS) ```

Question 27

which NOS forms are constitutive

Answer 27

eNOS | nNOS

Question 28

which forms of NOS have steady levels in th body

Answer 28

nNOS | eNOS

Question 29

where are eNOS and nNOS found in the body?

Answer 29

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

Question 30

how is iNOS induced?

Answer 30

by specific cytokines | often in response to inflammatory conditions

Question 31

product of nitrite oxidation with oxyhaemaglobin

Answer 31

nitrate

Question 32

product of nitric oxide directly reacting with oxyhaemaglobin

Answer 32

methhaemaglobin and nitrate

Question 33

most common nitrosylated product in plasma.

Answer 33

R-SNO

Question 34

why is production of S-nitrosothiols common

Answer 34

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

Question 35

what is the main storage form of nitric oxide

Answer 35

nitrate (most stable)

Question 36

role of caveolin-1

Answer 36

modulates NO production

Question 37

how is cGMP produced

Answer 37

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

Question 38

how does cGMP effect smooth muscles

Answer 38

Increased intracellular cGMP inhibits calcium entry into the cell --> decreased intracellular calcium concentration activation of myosin light chain kinase both causes smooth muscle relaxation

Question 39

when is caveolin-1 concentration increased

Answer 39

in cv disease states

Question 40

which type of blood vessel does nitric oxide effect the most

Answer 40

affects veins more than arteries | 80% of blood is found in veins so dilation of veins has bigger effect

Question 41

where is NO produced

Answer 41

vascular endothelium

Question 42

which types of NOS are calcium dependent

Answer 42

``` constitutive NOS (cNOS) (eNOS and nNOS) ```

Question 43

2 mechanisms to stimulate NO production

Answer 43

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

Question 44

2nd messenger in vasodilation

Answer 44

cyclic GMP - inhibits Ca2+ entry/activates K+ channels --> hyperpolarisation - activates myosin light chain phosphotase

Question 45

definition of bioavailabilty

Answer 45

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

Question 46

mechanism of cav-1

Answer 46

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

Question 47

bioavailability of orally ingested nitrates

Answer 47

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

Question 48

how does NOS contribute to oxidative stress in mitochondria

Answer 48

NO binds to COX enzyme (competes with oxygen) | results in partial inhibition of mitochondrial respiration

Question 49

effect of hypoxia

Answer 49

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

Question 50

BH4

Answer 50

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

Question 51

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

Answer 51

reduces bioavailability of NO

Question 52

what % of ingested inorganic nitrates is excreted in urine

Answer 52

60%

Question 53

what is sGC

Answer 53

soluble Guanylyl-cyclase

Question 54

role of facultative anaerobes after inorganic nitrates have been ingested

Answer 54

reduce NO3- to NO2- on the surface of the tongue | before NO2- is swallowed