Stress-related Diseases -- A Potential Role for Nitric Oxide

Med Sci Monit. 2002 Jun;8(6):RA103-18.


Nitric oxide (NO) is involved in stress physiology and stress-related disease processes. Like stress, NO seems to be capable of principally exerting either beneficial or deleterious effects. The actual distinction depends on a multitude of factors. Moreover, NO counteracts norepinephrine (NE) activity and sympathetic responsivity. Thus, NO and the stress (patho)physiology are closely connected and molecular mechanisms or pathways may be shared under certain conditions. NO is involved in immunological, cardiovascular, and neurodegenerative diseases/ mental disorders. It represents a 'double-edged sword', since small quantities produced by constitutive enzymes may predominantly mediate physiological effects, whereas the expression of inducible NO synthases may lead to larger quantities of NO, a situation that may be associated with cytotoxic and detrimental effects of NO. The key step for normally useful physiological mechanisms becoming pathophysiological may be represented by the loss of balance, the loss of control over the different pathways induced. A failure to terminate or shift originally protective mechanisms may lead to a vicious cycle of disease-supporting pathophysiological pathways.

Conclusions: Profound connections between stress and various disease processes exist. Thereby, common pathophysiological pathways in stress-related diseases have been described, and they involve stress hormone (cortisol, NE) and, in particular, NO activity. Thus, NO has detrimental capacities. However, NO not only exerts deleterious but also strongly ameliorating effects. The balance between both properties is crucial. Yet, nitric oxide involvement in stress-related diseases represents a common pathway, with various pathophysiological analogies, that may be accessible for strategies using stress management and relaxation response techniques.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / physiopathology
  • Humans
  • Mental Disorders / complications
  • Mental Disorders / physiopathology
  • Neurodegenerative Diseases / complications
  • Neurodegenerative Diseases / physiopathology
  • Nitric Oxide / physiology*
  • Signal Transduction
  • Stress, Physiological / complications
  • Stress, Physiological / immunology
  • Stress, Physiological / physiopathology*


  • Nitric Oxide