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Flashcards in Nitric Oxide Deck (50)
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1

What are 3 actions of NO?

1) relax smooth muscle
2) decrease cell adhesion
3) evoke inflammatory response

2

Endogenous nitric oxide is generated from the oxidation of the ___________ group of __________.

guanidine group of arginine

3

True or false: exposure of LPS results in generation of NO in the macrophage

TRUE

4

When is NO normally, physiologically released by the endothelium?

upon stimulation with Ach and carbachol

5

What is the role of NO in the face of injury?

counteracts vasoconstriction

6

What enzyme family makes NO?

nitric oxide synthase

7

Which form of NOS is inducible?

NOS-2

inTWOcible

8

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

9

What are the 2 endogenous, normal NOS?

NOS-1 and NOS-3

10

Which NOS is also called eNOS (found in the endothelial cells)?

NOS-3

3 rhymes with e

11

Which NOS is the neuronal NOS?

NOS-1 (brain is #1)

12

What is the substrate for NOS?

L-arginine

13

What inhibits NOS?

arginine analogues (N-monomethyl L-arginine)

14

How does nitroprusside differ from nitroglycerin?

nitroprusside: spontaneously generate NO

nitroglycerin: require presence of thiol compound such as cysteine

15

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

16

NOS converts arginine to ______________ and NO

citrulline

17

Once formed, NO can do what 2 things?

nitroslyate proteins (NO is a free radical) or complex with heme of guanylyl cyclase

18

The most stable form of nitric oxide is _____ and it is used as a measure for how much NO is produced

NO3

19

What inactivates NO?

heme and free radical superoxide

20

How does superoxide dismutase affect the duration of NO action?

prolongs it by scavenging superoxide, NO's inactivator

21

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

22

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

23

What is the danger of excess production of NO?

generation of peroxynitrite which is toxic to cells

24

Why are NO inhibitors important for the treatment of sepsis related disorders?

reduce formation of peroxynitrite

25

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

26

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

27

The beneficial effects of NO are __________________, ___________, and _______________

smooth muscle relaxation
vasodilation
immune regulation

28

The negative effects of NO are _____________

free radical formation, nitrosation, irritant effects

29

Decrease NO can result in _____________ blood pressures

elevated

30

What is the danger of NO interaction with sildenafil (viagra)?

viagra also increases cGMP by inhibiting phosphodiesterase (which converts cGMP to GMP) leading to massive amounts of cGMP/vasodilation