Trigger 4: NNN pathways

Question 1

Nitrate, nitrite and nitric oxide cycle

Answer 1

NO3 reduced to NO2- reduced to NO

Question 2

how is NO also produced

Answer 2

production of NO from L-arginine by NOS

Question 3

Entero-salivary circulation of dietary nitrate

Answer 3

1. Nitrate (blue) derived from the diet is swallowed
2. It is rapidly and completely absorbed in the upper gastrointestinal tract
3. Approx. 35% is concentrated in the salivary glands and secreted into the mouth
4. Here it is reduced to nitrite (red) by facultative anaerobes on the dorsum of the tongue and swallowed
5. Some of the nitrite undergoes acidic reduction to NO in the stomach
6. The rest is absorbed
7. 60% of ingested nitrate is lost in the urine within 48h

Question 4

Smooth muscle relaxation

Answer 4

1) increase in intracellular calcium
2) stimulates cNOS to convert L-arg to NO
3) NO diffuses into neighbouring smooth muscle cell
4) NO activate GC
5) GC activates GTP –> cGMP which activates MLCP
5) MLCP removes phosphatase from myosin light chain
6) smooth muscle relaxation

Question 5

all forms of NOS produce NO from

Answer 5

L-arginine

Question 6

Caveolin-1 and NO production

Answer 6

1. Increased expression of Caveolin-1 (CVD )
2. Increased inhibition of eNOS
3. Less NO produced
4. Decreased NO bioavailability
5. Reduction in NO-mediated vasodilation
   Endothelial dysfunction which promoted atherosclerosis

Question 7

describe the L-arginine oxide pathway

Answer 7

L+arginine and oxygen react, catalysed by NOS to produce NO

• oxidation leads to NO3/NO2

Question 8

describe simple NNN oxide pathway

Answer 8

1) nitrate taken in through diet
2) bacterial nitrate reductase (Xanthine oxidase) reduces NO3 to NO2
3) NO2- is reduced to NO2 via deoxygenated B, Xanthine oxidate, respiratory chain enzymes and protons

Question 9

3 effects of NO

Answer 9

• vasodilation
• reduced BP
• anti-inflammatory (at low level)
• anti-platlelt aggregation
• increased mitochondrial respiration

Question 10

inorganic nitrates structure

Answer 10

SIMPLE- no carbon e.g. NO2

Question 11

organic nitrate structure

Answer 11

much more complicated (has carbon0

Question 12

all organic nitrates are

Answer 12

medicinally synthesises

Question 13

inorganic nitrates are produced

Answer 13

endogenously (L-arginine)

Question 14

where else do we get inorganic nitrates

Answer 14

food e.g. beetroot

Question 15

in current clinical practice the term nitrate mainly refers to the use of

Answer 15

organic nitrates

Question 16

names an organic nitrate

Answer 16

glyceryl trinitrate (GTN)-§

Question 17

GTN is a

Answer 17

spray

Question 18

amyl nitrite

Answer 18

is an organic nitrate used to treat angina

Question 19

first known use of inorganic nitrate

Answer 19

as a preservative to cure food

Question 20

thought that organic and inorganic nitrates

Answer 20

exert a similar effect on vasculature

Question 21

key pathway for orally injected inorganic nitrates

Answer 21

enterosalivary circulation

Question 22

enterosalivary circulation

Answer 22

• prevent abrupt effect
• prevent toxic levels of nitrite
• prevents prolonged effects

Question 23

inorganic nitrates have a more ….. effect

Answer 23

subtle effect than organic nitrates

Question 24

benefits of inorganic nitrates over organic nitrates

Answer 24

no tolerance

Question 25

organic nitrates do not use

Answer 25

the enterosalivary circulation

Question 26

organic nitrates have

Answer 26

potent effects

Question 27

organic nitrates are limited by

Answer 27

individuals getting tolerance

Question 28

organic nitrates can cause

Answer 28

endothelial dysfunction

Question 29

endothelial dysfunction can trigger

Answer 29

production fo ROS- which aggravates tolerance