Nitric Oxide

INTRODUCTION:
  • Nitric oxide, a vasodilator is formed by the action of nitric oxide synthase on Arginine.
  • Present in low concentration in cigarette smokers
  • Synthesis:
  1. NO is formed by the action of Cytosolic enzyme NO synthase in endothelial & neuronal cells.
  2. Substrate: Arginine, O2, NADPH
  3. Coenzyme: NADPH, FAD, FMN, Heme, tetrahydrobiopterin
  4. Product: Citrulline, NO
BIOLOGICAL ROLE:
  • Nitric oxide has been demonstrated to play a role in a variety of biological processes including neurotransmission, immune defence, the regulation of cell death (apoptosis) and cell motility.
  • Inhaled nitric oxide is used For reducing pulmonary hypertension
  • Nitric oxide has been suggested to play an anti-inflammatory role by inhibiting the expression of the genes for inflammatory cytokines.
  • The primary action of the neurotransmitter Nitric oxide (NO) in the gastrointestinal tract is Gastrointestinal smooth muscle relaxation
  • NO has important role in producing penile erection by causing vasodilation and hence engorgement of corpora cavernosa.( Erection is caused by parasympathetic impulses that pass from sacral portion of spinal cord.These parasympathetic nerve fibres in contrast to most other parasympathetic fibres are believed to secrete nitric oxide and/or vasoactive intestinal peptide in addition to acetylcholine.)
  • Sildenafil, popularly known by the trade name Viagra, stimulates erections primarily by enhancing signaling through the nitric oxide pathway in the penis. Cigarette smoking decreases endogenous NO formation and hence increases the risk of cardiovascular disease through increased hypertension and platelet aggregation.
FEATURES:
  • Reacts with oxygen & superoxide peroxynitrite which decomposes to form highly reactive OH-radical
  • It stimulates guanyl cyclase (cGMP)
FUNCTIONS:
  • Relaxes smooth muscles(vascular tone)
  • Inhibit the lower esophageal sphincter
  • Prevents platelet aggregation
  • Nitric Oxide (NO) is a novel neurotransmitter which is condidered to have an effect in the pathophysiology of Mood Disorders
  • Functions as neurotransmitter in brain
  • Mediates tumoricidal, bactericidal actions of macrophages
  • Involved in penile erection; (sildenafil affects this process by inhibiting a cGMP dependent phosphodiesterase)
Subtype & Name Chromosome Comments Result of Gene Knockout in Mice
1 - nNOS (neuronal) 12 Activity depends on elevated Cat2+
First identified in neurons.
Calmodulin-activated
Pyloric stenosis, resistance tovascular stroke,
Aggressive sexual behavior (males)
2 - iNOS (inducible) 17 Independent of elevated Cat2+.prominent in macrophages More susceptible to certain typesof infection
3 - eNOs (endothelial 17 Activity depends on elevated Cat2+
First identified in endothelial cells.
Elevated mean blood pressure
1. Nitric oxide level is increased by increased release of donors
Acetylcholine
Aspirin (No releasing aspirin)
Glyceryltrinitrate
ACE inhibitor
Sodium nitroprusside
Calcium ions
Hydralazine
2. Drugs which inhibits phosphodiesterase enzyme
Slidenaphil
Aminophylline

Exam Question
  • 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 condidered 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 esophageal 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
Don't Forget to Solve all the previous Year Question asked on Nitric Oxide