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Paradoxical fate and biological action of peroxynitrite on human platelets.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Read, N. G. Moro, M. A. Goodwin, D. A. Feelisch, M. Zamora-pino, R. Moncada, S. Darley-usmar, V. M. Radomski, M. W.
Description	Author Affiliation: Moro MA ( Wellcome Research Laboratories, Langley Court, Beckenham, Kent, United Kingdom.);
Abstract	Peroxynitrite (ONOO-), which is formed from the reaction of nitric oxide (NO) and superoxide (O2-), has been suggested to be responsible for some of the cytotoxic effects of these molecules. When protonated, ONOO- gives rise to hydroxyl (OH.) and nitrogen dioxide (NO2) radicals, which are capable of inducing tissue damage. We have investigated the effects of ONOO- on human platelets in vitro in order to explore the potential of this oxidant to contribute to tissue damage. ONOO- caused aggregation of washed platelets and reversed the inhibition of aggregation induced by S-nitroso-N-acetyl-DL-penicillamine (SNAP), prostacyclin, and indomethacin. However, in platelet-rich plasma, ONOO- not only did not possess proaggregatory properties but acted as an inhibitor of platelet aggregation. This reversal of the aggregatory effect of ONOO- could also be achieved in washed platelets by adding low concentrations of plasma, human serum albumin, or glutathione and was inhibited by hemoglobin. An analysis of the reaction products of ONOO- and glutathione revealed the presence of both NO and S-nitrosoglutathione in quantities sufficient to account for the antiaggregatory effects observed. Thus the fate and therefore the actions of ONOO- in biological systems are critically dependent on the biological environment in which this oxidant is present.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	14
Volume Number	91
Language	English
Publisher	National Academy of Sciences
Publisher Date	1994-08-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Blood Platelets Physiology Nitrates Blood Pharmacology Platelet Aggregation Antigens, CD Drug Effects Ultrastructure Cell Adhesion Molecules Collagen Epoprostenol Glutathione Analogs & Derivatives Hemoglobins In Vitro Techniques Indomethacin Kinetics Nitroso Compounds P-Selectin Penicillamine Platelet Membrane Glycoproteins S-Nitroso-N-Acetylpenicillamine S-Nitrosoglutathione Serum Albumin Time Factors Vasodilator Agents Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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