Nitric oxide and oxygen radicals: a question of balance

Abstract

The production of superoxide and nitric oxide individually has been associated with the development of several diseases but only recently has it been realised that interactions between them may also be important in disease pathology. The central hypothesis which is emerging is that the balance between nitric oxide and superoxide generation is a critical determinant in the aetiology of many human diseases including atherosclerosis, neurodegenerative disease, ischaemia-reperfusion and cancer. These ideas are discussed in this short overview and placed in the context of the current and future status of therapies which could modulate the balance between nitric oxide and superoxide.

Protection against peroxynitrite‐dependent tyrosine nitration and α1‐antiproteinase inactivation by oxidized and reduced lipoic acid

“…Recently, there has been considerable interest in reactive nitrogen species as mediators of tissue injury [9,10]. Although nitric oxide (NO') has many important physiological functions [11], its production in excess may contribute to the pathology of neurodegenerative disease, chronic inflammation, acute respiratory distress syndrome, atherosclerosis and septic shock [9][10][11][12][13][14].…”

“…Although nitric oxide (NO') has many important physiological functions [11], its production in excess may contribute to the pathology of neurodegenerative disease, chronic inflammation, acute respiratory distress syndrome, atherosclerosis and septic shock [9][10][11][12][13][14]. Part of the toxicity of NO" involves its reaction with superoxide radical (02 °-) to give peroxynitrite, ONOO-…”

“…Peroxynitrite induces peroxidation of lipids, oxidizes methionine and -SH residues in proteins, depletes antioxidants and causes DNA damage [9,10,15,16]. In particular, addition of peroxynitrite to biological fluids leads to nitration of tyrosine residues, and the presence of these appears to be a 'marker' of peroxynitrite-dependent damage in vivo [10,[12][13][14][15][16].…”

“…Hence peroxynitrite generation in vivo can facilitate both oxidative and proteolytic damage [9,10,18].…”

Antioxidant protection: yet another function of endothelial progenitor cells?

“…The rapidity of the reaction between O 2 À and NO, and between O 2 À and the SOD, would suggest that in compartments where these three entities coexist, there could be interactions such that alterations in the amounts of either O 2 À or SOD that could markedly alter levels of NO. 22 In this issue of Journal of Human Hypertension, Tao et al 23 demonstrate the in vitro capacity of cultured EPCs to enhance SOD production in response to shear stress. This is one of the first papers to show that in vitro shear stress enhances mRNA expression and activity of Cu/Zn SOD in human EPCs, suggesting that shear stress can be used as a novel manipulation means to improve the functional potential of EPCs.…”