CHAPTER 19: NITRIC OXIDE

Source of Nitric oxide: Nitroglycerin

MOA: Nitric oxide donor

Enzymes:
1. Neuronal NOS (nitric oxide synthase)
Calcium dependent
2. Endothelial NOS
3. Inducible NOS/ macrophage- not calcium dependent

3 Target of Nitric Oxide:

1. Metalloproteins
-initial reaction of NO
2. Thiols (all compounds that contain Sulfur)
-S nitrosylation (reaction/ process with regards to NO & S containing
compounds)
Product: GSH
3. Tyrosine
-Tyrosine Nitration: formation of superoxide (powerful oxidants)
Product: Superoxide

GSH (glutathione): Major intracellular sulfur containing compound

- scavenger of superoxides

Aldehyde reductase
Nitroglycerin Nitric Oxide
Heme of guanylyl cyclase

Activation of guanylyl cyclase

GTP

cGMP
Vasodilators
PKG

Thus, NO does not directly cause

vasodilation

NO: increase cGMP & PKG

Effects of NO:
A. Vasodilation- used in hypertension
B. Antioxidant- ex. Glutathione (s-nitrosylation)
Nitrosoglutathione= NO + Glutathione
-stable form of nitric oxide
-antioxidant
C. Decreases platelet aggregation
NO: prevent formation of foam cells in arterialwall/ cholesterol plaque

1.ORGANIC NITRATES
ISOSORBIDE DINITRATE
BN: Isordil
-metabolized to NO
-with continous use; effectivity will decrease (Nitrate Tolerance)

2.ORGANIC NITRITES
ISOAMYL NITRITE

3.SODIUM NITROPRUSSIDE (Emergency use only)

-rapid reduction of BP
-used for hypertensive emergencies

4. NO GAS INHALATION

5. SILDENAFIL (not a NO donor) Action of Phosphodiesterase inhibitor:

BN: Viagra Prolongs effect cGMP
MOA: 5 Phohphodiesterase inhibitor More vasodilation
Does not cause direct increase of cGMP

NITRIC OXIDE IN DISEASE

Septicemia- iNOS will be triggered (induced by the infection)

=dilation of blood vessel
=low BP; normal blood volume

How to reverse hypotension in Sepsis?

-prevent action of NO by scavenging of NO by hemoglobin

Hemoglobin: scavenger of NO

Inhalation type of NO: reduced pulmonary hypertension