This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ferdinandy, P. Articles by Schulz, R. Search for Related Content PubMed PubMed Citation Articles by Ferdinandy, P. Articles by Schulz, R.

(Circulation Research. 2001;88:e12.)
© 2001 American Heart Association, Inc.

Letter to the Editor

Peroxynitrite: Toxic or Protective in the Heart?

Péter Ferdinandy¹

¹ Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Szeged, Hungary

Richard Schulz²

² Cardiovascular Research Group, Departments of Pediatrics and Pharmacology, University of Alberta, Edmonton, Alberta, Canada, richard.schulz@ualberta.ca

	Peroxynitrite: Toxic or Protective in the Heart?

 
To the Editor:

The literature is somewhat controversial as to whether peroxynitrite (ONOO^–) is either cytotoxic or cytoprotective. An Editorial by Vinten-Johansen¹ recently suggested that deleterious effects of ONOO^– in the heart are predominantly observed in in vitro or ex vivo crystalloid buffer–perfused systems; however, ONOO^– is cardioprotective if applied in vivo. Does the exogenous administration of ONOO^– accurately reflect pathological conditions in which the endogenous generation of ONOO^– within cells is enhanced?

Because of the short half-life of ONOO^– at physiological pH, it has very little chance to reach its cellular targets when it is applied via the blood, as it rapidly reacts with plasma proteins and thiols such as glutathione and cysteine. Thus, ONOO^– is likely to be detoxified before it has a chance to reach tissues downstream of the injection site, let alone the intracellular compartment.² ONOO^– forms S-nitrosothiols when it combines with thiol groups,³ which then act as nitric oxide (NO) donors. Because NO itself is a cardioprotective and antioxidant molecule,⁴ protection from noxious stimuli may result when exogenous ONOO^– is administered intravenously. Accordingly, exogenously administered ONOO^– was shown to inhibit leukocyte-endothelial cell interactions and to protect against ischemia/reperfusion injury in rats in vivo.⁵ Intraventricular infusion of ONOO^– reduced myocardial infarct size and preserved coronary endothelium after ischemia and reperfusion in cats,⁶ an effect that was mediated by the intermediate formation of S-nitrosothiols.⁷

Exogenously applied ONOO^–, however, has been shown to be detrimental to cellular functions when it was applied in crystalloid . . . [Full Text of this Article]

This article has been cited by other articles:

				C. Dezfulian, N. Raat, S. Shiva, and M. T. Gladwin Role of the anion nitrite in ischemia-reperfusion cytoprotection and therapeutics Cardiovasc Res, July 15, 2007; 75(2): 327 - 338. [Abstract] [Full Text] [PDF]

				A. K. Grover, C.-Y. Kwan, and S. E. Samson Effects of peroxynitrite on sarco/endoplasmic reticulum Ca2+ pump isoforms SERCA2b and SERCA3a Am J Physiol Cell Physiol, December 1, 2003; 285(6): C1537 - C1543. [Abstract] [Full Text] [PDF]