Flashcards in Nitric Oxide Deck (50)
What are 3 actions of NO?
1) relax smooth muscle
2) decrease cell adhesion
3) evoke inflammatory response
Endogenous nitric oxide is generated from the oxidation of the ___________ group of __________.
guanidine group of arginine
True or false: exposure of LPS results in generation of NO in the macrophage
When is NO normally, physiologically released by the endothelium?
upon stimulation with Ach and carbachol
What is the role of NO in the face of injury?
What enzyme family makes NO?
nitric oxide synthase
Which form of NOS is inducible?
What does it mean to be for NOS to be inducible?
triggered by disease (like sepsis)
NOS-2 is in macrophages and smooth muscle cells
What are the 2 endogenous, normal NOS?
NOS-1 and NOS-3
Which NOS is also called eNOS (found in the endothelial cells)?
3 rhymes with e
Which NOS is the neuronal NOS?
NOS-1 (brain is #1)
What is the substrate for NOS?
What inhibits NOS?
arginine analogues (N-monomethyl L-arginine)
How does nitroprusside differ from nitroglycerin?
nitroprusside: spontaneously generate NO
nitroglycerin: require presence of thiol compound such as cysteine
What is the mechanism of action of NO?
interacts with heme moiety of soluble guanyl cyclase in cytoplasm of cell
guanyl cyclase converts GTP to cGMP
NOS converts arginine to ______________ and NO
Once formed, NO can do what 2 things?
nitroslyate proteins (NO is a free radical) or complex with heme of guanylyl cyclase
The most stable form of nitric oxide is _____ and it is used as a measure for how much NO is produced
What inactivates NO?
heme and free radical superoxide
How does superoxide dismutase affect the duration of NO action?
prolongs it by scavenging superoxide, NO's inactivator
How does glutathione play a role in NO regulation?
glutathione regulates peroxynitrile which is the product of NO and superoxide
peroxynitrile complexes with sulfhydral group of many key enzymes
WANT HIGH LEVELS OF GLUTATHIONE TO MITIGATE DANGEROUS NO FORMATIONS
What are 4 ways to inhibit NO?
1) L-arginine derivatives (block formation of NO)
2) inhibitors of nitric oxide synthase
3) inhibitor of binding of arginine to NO
4) scavenger of NO
What is the danger of excess production of NO?
generation of peroxynitrite which is toxic to cells
Why are NO inhibitors important for the treatment of sepsis related disorders?
reduce formation of peroxynitrite
NO's major effects are mediated by the activation of _______ _______ which results in the generation of _______.
guanyl cyclase resulting in the generation of cyclic GMP
In addition to activating guanylyl cyclase, NO can generate several reactive nitrogen derivatives by interacting with molecular radicals. Why are these oxides dangerous?
they are highly reactive and unstable and alter the physio disposition of cells and tissues
The beneficial effects of NO are __________________, ___________, and _______________
smooth muscle relaxation
The negative effects of NO are _____________
free radical formation, nitrosation, irritant effects
Decrease NO can result in _____________ blood pressures