Trigger 4: NNN pathways Flashcards
Nitrate, nitrite and nitric oxide cycle
NO3 reduced to NO2- reduced to NO
how is NO also produced
production of NO from L-arginine by NOS
Entero-salivary circulation of dietary nitrate
- Nitrate (blue) derived from the diet is swallowed
- It is rapidly and completely absorbed in the upper gastrointestinal tract
- Approx. 35% is concentrated in the salivary glands and secreted into the mouth
- Here it is reduced to nitrite (red) by facultative anaerobes on the dorsum of the tongue and swallowed
- Some of the nitrite undergoes acidic reduction to NO in the stomach
- The rest is absorbed
- 60% of ingested nitrate is lost in the urine within 48h
Smooth muscle relaxation
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
all forms of NOS produce NO from
L-arginine
Caveolin-1 and NO production
- Increased expression of Caveolin-1 (CVD )
- Increased inhibition of eNOS
- Less NO produced
- Decreased NO bioavailability
- Reduction in NO-mediated vasodilation
Endothelial dysfunction which promoted atherosclerosis
describe the L-arginine oxide pathway
L+arginine and oxygen react, catalysed by NOS to produce NO
- oxidation leads to NO3/NO2
describe simple NNN oxide pathway
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
3 effects of NO
- vasodilation
- reduced BP
- anti-inflammatory (at low level)
- anti-platlelt aggregation
- increased mitochondrial respiration
inorganic nitrates structure
SIMPLE- no carbon e.g. NO2
organic nitrate structure
much more complicated (has carbon0
all organic nitrates are
medicinally synthesises
inorganic nitrates are produced
endogenously (L-arginine)
where else do we get inorganic nitrates
food e.g. beetroot
in current clinical practice the term nitrate mainly refers to the use of
organic nitrates
names an organic nitrate
glyceryl trinitrate (GTN)-§
GTN is a
spray
amyl nitrite
is an organic nitrate used to treat angina
first known use of inorganic nitrate
as a preservative to cure food
thought that organic and inorganic nitrates
exert a similar effect on vasculature
key pathway for orally injected inorganic nitrates
enterosalivary circulation
enterosalivary circulation
- prevent abrupt effect
- prevent toxic levels of nitrite
- prevents prolonged effects
inorganic nitrates have a more ….. effect
subtle effect than organic nitrates
benefits of inorganic nitrates over organic nitrates
no tolerance
