Nitric Oxide
- Vasodilator.
- Formed by action of nitric oxide synthase on Arginine.
Steps in synthesis:
- NO formed by cytosolic enzyme NO synthase action on endothelial & neuronal cells.
- Substrate: Arginine, O2, NADPH
- Coenzyme: NADPH, FAD, FMN, Heme, tetrahydrobiopterin
- Product: Citrulline, NO.
- Present in low concentration in cigarette smokers
BIOLOGICAL ROLE:
In biological processes like,
- Neurotransmission.
- Immune defence.
- Cell death (apoptosis) regulation.
- Cell motility.
Inhaled nitric oxide – Reduces pulmonary hypertension
- Anti-inflammatory role.
- By inhibiting genes expression of inflammatory cytokines.
- As a neurotransmitter in GI tract
- Causes gastrointestinal smooth muscle relaxation.
- Produces penile erection.
- By causing vasodilation & engorgement of corpora cavernosa.
- No released from parasympathetic nerve fibres.
- Eg: Viagra – Stimulates erection by enhancing nitric oxide pathway signaling within penis.
- Cigarette smoking decreases endogenous NO formation.
- Increases risk of CVS disease through hypertension & platelet aggregation.
- Reacts with oxygen & superoxide peroxynitrite which decomposes forming highly reactive OH- radicals.
- Stimulates cGMP.
FUNCTIONS:
- Relaxes smooth muscles (vascular tone)
- Inhibits lower esophageal sphincter
- Prevents platelet aggregation
- As a Neurotransmitter.
- Effect on Mood Disorders.
- Mediates tumoricidal & bactericidal actions of macrophages
- Involved in penile erection.
- Sildenafil counteracts this by inhibiting cGMP dependent phosphodiesterase.
|
Subtype & Name |
Chromosome |
Comments |
Result of Gene Knockout in Mice |
|
n-NOS (neuronal) |
12 |
Activity depends on elevated Ca2+. First identified in neurons. Calmodulin-activated |
Pyloric stenosis, resistance to vascular stroke, Aggressive sexual behaviour (males) |
|
i-NOS (inducible) |
17 |
Independent of elevated Cat2+. prominent in macrophages |
More susceptible to certain types of infection |
|
e-NOs (endothelial |
17 |
Activity depends on elevated Cat2+. First identified in endothelial cells. |
Elevated mean blood pressure |
|
Nitric oxide level increased |
|
Acetylcholine Aspirin Glyceryl trinitrate ACE inhibitor Sodium nitroprusside Calcium ions Hydralazine |
|
Drugs which inhibits phosphodiesterase enzyme |
|
Sildenafil Aminophylline |
- Nitric oxide is produced from endothelium.
- Nitric oxide helps to regulate vascular tone & shows important role in penile erection.
- Present in low concentration in cigarette smokers.
- Nitric Oxide (NO) is a novel neurotransmitter which is considered to have an effect in the pathophysiology of Mood Disorders.
- Nitric oxide is synthesised from arginine.
- Nitric oxide is an important mediator of vasodilation.
- The primary action of the neurotransmitter Nitric oxide (NO) in the gastrointestinal tract is gastrointestinal smooth muscle relaxation.
- Vasoactive intestinal polypeptide and nitric oxide inhibit the lower oesophagal sphincter.
- Mechanism of action of Nitric oxide is through cGMP.
- Drugs which increases nitric oxide are Glycerine trinitrate, Hydralazine, Sodium nitroprusside.
- Inhaled nitric oxide is used for reducing pulmonary hypertension.
- Platelet adhesion is inhibited by Nitric oxide.
- Inhaled nitric oxide is used to decrease pulmonary artery pressure in adults and infants.
