The formation of nitric oxide donors from peroxynitrite

María Ángeles Moro, Victor M. Darley‐Usmar, Ignacio Lizasoain, Yunchao Su, Richard G. Knowles, Salvador Moncada, Marek W. Radomski

Research output: Contribution to journalArticle

176 Scopus citations

Abstract

Administration of peroxynitrite (ONOO, 30–300 μM) caused relaxation of rabbit aortic strips superfused in series in a cascade. The compound responsible for this effect had a half‐life greater than 20 s and could not therefore be either nitric oxide (NO) or ONOO which have half‐lives in the order of 1–2 s under these conditions. However the relaxation was inhibited by oxyhemoglobin, suggesting that the compound could be converted to NO in the vascular tissues or in the superfusate. The products of the reaction between ONOO and Krebs buffer containing 11 mM glucose, but not glucose‐free Krebs buffer, caused relaxation of the bioassay tissues. These data suggest that stable NO donor(s) were formed from the reaction of ONOO with glucose. We therefore prepared these NO donor(s) by the reaction of glucose solutions with ONOO in order to characterize their pharmacological actions both in the cascade bioassay and on platelets and to study their ability to release NO. These reaction product(s) caused relaxation in the cascade and inhibition of platelet aggregation. Both effects were dependent on the concentration of D‐glucose, were equally effective if L‐glucose was used as a reactant and were reversed by oxyhaemoglobin. The products of the reaction between ONOO and glucose or other biological molecules containing an alcohol functional group, such as fructose, glycerol, or glyceraldehyde, released NO in the presence of Cu2+ and L‐cysteine. These results indicate that ONOO reacts with sugars or other compounds containing an alcohol functional group(s) to form NO donor(s) with the characteristics of organic nitrate/nitrites. This may represent a further detoxification pathway for ONOO in vivo. 1995 British Pharmacological Society

Original languageEnglish (US)
Pages (from-to)1999-2004
Number of pages6
JournalBritish Journal of Pharmacology
Volume116
Issue number3
DOIs
StatePublished - Oct 1995

Keywords

  • Nitric oxide
  • glucose
  • oxidative stress
  • peroxynitrite
  • platelets
  • vascular wall

ASJC Scopus subject areas

  • Pharmacology

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    Moro, M. Á., Darley‐Usmar, V. M., Lizasoain, I., Su, Y., Knowles, R. G., Moncada, S., & Radomski, M. W. (1995). The formation of nitric oxide donors from peroxynitrite. British Journal of Pharmacology, 116(3), 1999-2004. https://doi.org/10.1111/j.1476-5381.1995.tb16404.x