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Flashcards in Nitric Oxide Deck (32):
1

NO is also known as...?

EDRF
Endothelium Derived Relaxation Factor

2

List some pharmacological effects of NO

Smooth muscle relaxation
Vasodilation
Decreased cell adhesion

Inflammatory Response in excess production

3

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

4

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.

5

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

6

Which NOS enzymes are constitutive and inducible?

NOS2 is inducible (pathological)

NOS1/3 are constitutive/housekeeping enzymes

7

Where is NOS1 located?

Neuronal epithelial cells

8

Where is NOS2 located?

Macrophages and smooth muscle cells

9

Where is NOS3 located?

Endothelial cells

10

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

11

NO Functions

-Binds heme moiety of guanylyl cyclase to make cGMP.
-Nitrosylates tyrosine and cysteine because NO is a free radical

12

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

13

What effect would superoxide dismutase have on NO?

May increase NO's potency and increase its duration

14

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

15

What are the main inhibitors of NOS?

L-arginine derivatives (such as NMMA, L-NAME) that will competitively bind NOS and inhibit NO production

16

NO and NO derivatives
Beneficial Pharmacological Effects

Vasodilation
Immune regulation
Anesthesia
Anti-atherosclerosis

17

Sildenafil
MOA

Inhibit phosphodiesterase.
Allows more cGMP to cause relaxation of blood vessels.

18

Toxic interactions of sildenafil

Do NOT take sildenafil with nitrates because this combination could cause severe hypotension and shock

19

Respiratory Effects of NO

Improves cardiopulmonary function in pulm HTN

Acts as a bronchodilator

20

Anti-atherosclerosis effects of NO

Inhibits adhesion molecules generation
Inhibit plaque formation
Inhibit homing of WBCs to plaque

21

What NO drugs should be given in treatment of atherosclerotic disorders?

Give L-arginine and NO Donors to allow for more NO production in atherosclerosis

22

NO
Effects on Platelets

Inhibitor of platelet aggregation, adhesion, activation

NO directly enhances fibrinolysis
Increases prostacyclin production

23

Why is NO helpful in organ transplants?

NO is cytoprotective and prevents cellular/platelet adhesion. Dietary arginine supplements are helpful in organ transplant patients.

24

What kind of neurons release NO in the peripheral NS?

NANC Neurons (Non adrenergic, Non cholinergic)

25

Nitrates primarily serve as...?

NO Donors that cause smooth muscle relaxation

26

Nitrates MOA

Release endogenous NO
Stimulation of guanylyl cyclase
Increase cGMP production
Smooth muscle relaxation

27

List some NO Donor Drugs

Nitroglycerin
Hydralazine
L-arginine

28

Nitroglycerine
Indication

Pulmonary Artery Hypertension

29

Hydrlazine
Indication

Hypertension

30

L-arginine Indications

Acute coronary syndrome
Vascular disease

31

Nitric Oxide (INOMAX)
Indications

Acute coronary syndrome

32

Sildenafil
Indications

HTN
ED

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