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

175 Citations (Scopus)

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 - Jan 1 1995
Externally publishedYes

Fingerprint

Peroxynitrous Acid
Nitric Oxide Donors
Nitric Oxide
Glucose
Oxyhemoglobins
Biological Assay
Buffers
Alcohols
Glyceraldehyde
Nitrites
Fructose
Platelet Aggregation
Nitrates
Glycerol
Blood Vessels
Half-Life
Blood Platelets
Pharmacology
Rabbits

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this

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

The formation of nitric oxide donors from peroxynitrite. / Moro, María Ángeles; Darley‐Usmar, Victor M.; Lizasoain, Ignacio; Su, Yunchao; Knowles, Richard G.; Moncada, Salvador; Radomski, Marek W.

In: British Journal of Pharmacology, Vol. 116, No. 3, 01.01.1995, p. 1999-2004.

Research output: Contribution to journalArticle

Moro, MÁ, Darley‐Usmar, VM, Lizasoain, I, Su, Y, Knowles, RG, Moncada, S & Radomski, MW 1995, 'The formation of nitric oxide donors from peroxynitrite', British Journal of Pharmacology, vol. 116, no. 3, pp. 1999-2004. https://doi.org/10.1111/j.1476-5381.1995.tb16404.x
Moro MÁ, Darley‐Usmar VM, Lizasoain I, Su Y, Knowles RG, Moncada S et al. The formation of nitric oxide donors from peroxynitrite. British Journal of Pharmacology. 1995 Jan 1;116(3):1999-2004. https://doi.org/10.1111/j.1476-5381.1995.tb16404.x
Moro, María Ángeles ; Darley‐Usmar, Victor M. ; Lizasoain, Ignacio ; Su, Yunchao ; Knowles, Richard G. ; Moncada, Salvador ; Radomski, Marek W. / The formation of nitric oxide donors from peroxynitrite. In: British Journal of Pharmacology. 1995 ; Vol. 116, No. 3. pp. 1999-2004.
@article{a2b99d961a3c4b44bda9773c09a6a166,
title = "The formation of nitric oxide donors from peroxynitrite",
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",
keywords = "Nitric oxide, glucose, oxidative stress, peroxynitrite, platelets, vascular wall",
author = "Moro, {Mar{\'i}a {\'A}ngeles} and Darley‐Usmar, {Victor M.} and Ignacio Lizasoain and Yunchao Su and Knowles, {Richard G.} and Salvador Moncada and Radomski, {Marek W.}",
year = "1995",
month = "1",
day = "1",
doi = "10.1111/j.1476-5381.1995.tb16404.x",
language = "English (US)",
volume = "116",
pages = "1999--2004",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - The formation of nitric oxide donors from peroxynitrite

AU - Moro, María Ángeles

AU - Darley‐Usmar, Victor M.

AU - Lizasoain, Ignacio

AU - Su, Yunchao

AU - Knowles, Richard G.

AU - Moncada, Salvador

AU - Radomski, Marek W.

PY - 1995/1/1

Y1 - 1995/1/1

N2 - 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

AB - 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

KW - Nitric oxide

KW - glucose

KW - oxidative stress

KW - peroxynitrite

KW - platelets

KW - vascular wall

UR - http://www.scopus.com/inward/record.url?scp=0029119947&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029119947&partnerID=8YFLogxK

U2 - 10.1111/j.1476-5381.1995.tb16404.x

DO - 10.1111/j.1476-5381.1995.tb16404.x

M3 - Article

VL - 116

SP - 1999

EP - 2004

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 3

ER -