Nitric oxide: the body's
wonder molecule1


Nitric oxide's diverse role in
biologic functions

"A startlingly simple molecule unites
neuroscience, physiology, and
immunology and revises scientists'
understanding of how cells communicate
and defend themselves."
 
 
— Science, 1992


The discovery of the role of nitric oxide (NO) as fundamental to biologic function was so remarkable that hundreds of research papers led Nitric Oxide to be proclaimed "molecule of the year" in 1992 by the journal Science. Three NO researchers shared the 1998 Nobel Prize in Medicine for their discovery that what had previously been known as EDRF (endothelium-derived relaxing factor) was, in fact, NO.

Evidence of its fundamental role began to emerge when scientists from distinct disciplines—immunology, cardiovascular physiology, and oncology—suddenly understood that they were studying the same molecule.

Nitric Oxide is highly reactive and diffuses freely across membranes, but has a lifetime of only a few seconds. This combination of properties makes it an ideal signaling molecule both between adjacent cells and within a single cell.

Nitric Oxide is produced by many different types of cells. Its function varies depending on where it’s produced. Those producer cells and functions include:


Innermost cell layer of arteries (the endothelium)

  • Spreads to artery muscle cells and stops contraction

Nerve cells

  • Modulates functions from behavior to gastrointestinal motility

White blood cells (macrophages)

  • Acts against bacteria and parasites

Brain

  • Acts as a neurotransmitter

Medical applications of nitric oxide

The novel properties of nitric oxide and its broad role in physiological processing mean that there is enormous potential for its use in many human healthcare areas, including:


Potential Nitric Oxide Therapy Areas1,2


Vasoregulatory

Pulmonary hypertension relief, erectile dysfunction, wound healing, etc.

Antimicrobial

Control of a broad range of pathogens

Anti-inflammatory

Pain, rheumatoid arthritis, eczema, cystic acne, etc.

Nitric oxide in wound care

NO plays an important role in multiple pathways of wound healing. The multiple actions of Nitric Oxide enhance wound strength and minimize scarring.


Anti-inflammatory
Effects
NO4-7
Antimicrobial
Effects of
NO4-8
Vasoregulatory
Effects of
NO4,5,7
Application of NO
Application of NO
Application of NO
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Upregulation endogenous
NO, growth factors, cytokines
Damage to bacterial
DNA at site injury
Upregulation of
vasoactive molecules
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Recruitment of
anti-inflammatory factors
to site of damage
DNA damage
prevents
bacterial replication
BV dilation,
increased permeability,
angiogenesis
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Inhibition of
inflammation
Inactivation of
infection
Increased blood flow
to site of damage
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Healing and regeneration of healthy tissue
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Challenges of therapeutic delivery of nitric oxide

NO can be delivered topically, orally, or by inhalation, but its short half-life (only a few seconds) can make it challenging to maintain its stability long enough to have a clinical effect. The most important question about NO delivery is: how can we deliver it therapeutically at the targeted site?


Top

References: 1. Culotta E and Koshland DE Jr. NO news is good news. Science. 1992;258:1862-1865. 2. Carpenter AW and Schoenfisch. Nitric oxide release part II: therapeutic applications. Chem Soc Rev. 2012;41(10):3742-3752. 3. Huerta S. Nitric oxide for cancer therapy. Future Sci OA. 2015:1(1), FS044. 4. Luo J, et al. Acta Pharmacologica Sinica. 2005;26(3):259–264. 5. Shekhter AB, et al. Bull Expt Biol and Medicine. 1998;126:829-824. 6. Schekhter AB, et al. Nitric Oxide. 2005;12(4):210-219. 7. Fang FC. Nat Rev Microbiol. 2004;2(10):820-832. 8. Treadwell T, et al. Poster presented at : The Symposium of Advanced Wound Care (SAWC); April 23-27, 2014 Orlando, FL.