Nitric Oxide Flashcards
NO is also known as…?
EDRF
Endothelium Derived Relaxation Factor
List some pharmacological effects of NO
Smooth muscle relaxation
Vasodilation
Decreased cell adhesion
Inflammatory Response in excess production
NO is produced by what enzymes? What is the substrate and other product of NO synthesis?
NOS (nitric oxide synthase) takes arginine and converts it to citrulline and NO
How does sepsis affect NO production?
Exposure to bacterial endotoxin (LPS) can activates inducible NOS, which causes vasodilation and potentially hypotension in patients with sepsis.
When the vessels are stimulated by acetylcholine and carbachol, how do they respond?
They vasoconstrict in response to Ach and carbachol, but the endothelium will then make and release NO to help vasodilate again and maintain blood flow
Which NOS enzymes are constitutive and inducible?
NOS2 is inducible (pathological)
NOS1/3 are constitutive/housekeeping enzymes
Where is NOS1 located?
Neuronal epithelial cells
Where is NOS2 located?
Macrophages and smooth muscle cells
Where is NOS3 located?
Endothelial cells
Once generated, how does NO produce smooth muscle relaxation?
Interacts with the heme moiety of guanylyl cyclase, converting GTP to cGMP, which is cytoprotective and causes relaxation of muscles
NO Functions
- Binds heme moiety of guanylyl cyclase to make cGMP.
- Nitrosylates tyrosine and cysteine because NO is a free radical
There are many products of redox reactions on NO. List the two most important pharmacologically
Nitrous Oxide (N2O) = Gaseous anesthetic
Nitrate (NO3-) = Used to measure how much NO a person has in their blood
What effect would superoxide dismutase have on NO?
May increase NO’s potency and increase its duration
What effect would glutathione have on NO?
Low glutathione level may contribute to vascular pathology. Endogenous glutathione may help reduce the toxic effects of excessive NO
What are the main inhibitors of NOS?
L-arginine derivatives (such as NMMA, L-NAME) that will competitively bind NOS and inhibit NO production
