Nitric Oxide in Human Health and Disease

  1. Sarti Paolo

Published Online: 15 APR 2013

DOI: 10.1002/9780470015902.a0003390.pub2



How to Cite

Paolo, S. 2013. Nitric Oxide in Human Health and Disease. eLS. .

Author Information

  1. Sapienza University of Rome, Rome, Italy

Publication History

  1. Published Online: 15 APR 2013


Nitric oxide (NO) is a free radical, actively produced in human body. NO exerts crucial roles in vascular and neuronal signal transduction, smooth muscle contractility, bioenergetics, platelet adhesion and aggregation, immunity, and cell death regulation. The evidence accumulated over the last 25 years suggests that a defective control of the NO levels causes pathologies, such as hypertension, cardiovascular dysfunctions, neurodegeneration, arthritis, asthma and septic shock. Despite dealing with NO, the boundary between health and disease is still blurry, although the feeling is that pulses of NO in the low concentration range (piconanomolar) are by and large physiological, whereas cell persistence in the high concentration range (micromolar) may turn to pathological. Evidence is growing that the dark side of NO resides on its concentration levels and on the production of peroxynitrite and other reactive oxygen and nitrogen species; last but not least, the type of biomolecule reacting with NO and, when present, the cell bioenergetic changes induced strongly contribute to physiological or pathological outcomes.

Key Concepts:

  • Nitric oxide shares with O2 and towards biomolecules, high reactivity and duality of effects, both beneficial and detrimental.

  • In the human body, a variety of metabolic effects are induced by NO, owing to the widespread nitrergic signalling and bioenergetic chemistry.

  • It is time to verify whether the S-nitrosation of proteins and enzymes is as important as their phosphorylation.

  • The NO chemistry in the human body appears tightly integrated with the chemistry of H2S and CO.

  • The intracellular NO and O2−• concentration, both absolute and relative, are vital to cell redox homoeostasis: it is their imbalance that triggers pathological responses.

  • Sometimes, the NO released by one isoform antagonises the effects of NO produced by another isoform. During cerebral ischaemia, for instance, the nNOS appears involved in tissue injury, whereas the eNOS preserves blood flow and tissue oxygenation.

  • The mechanism of macromolecular damage by peroxynirite is still poorly understood.

  • Feeling is growing that besides the oxidative stress, a reductive stress should be also considered.

  • For how long should a cell Ca++ transient lasts to stimulate cNOS? Moreover, is amplitude and duration of such a stimulus different in physiology and pathology?


  • radical chemistry;
  • nitrosative stress;
  • bioenergetics;
  • nitrergic transmission;
  • neurodegeneration;
  • mitochondria;
  • haem proteins pathophysiology;
  • warburg effect;
  • melatonin;
  • molecular mechanisms