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11:28
Analytical Techniques for Assaying Nitric Oxide Bioactivity
Published on: June 18, 2012
Heparin reacts with and inactivates nitric oxide
G R Upchurch1, D G Goodman, S R Willoughby
1Whitaker Cardiovascular Institute, Evans Department of Medicine, Boston University School of Medicine, MA 02118, USA.
Journal of Cardiovascular Pharmacology and Therapeutics
|August 18, 2001
Summary
Heparin can interfere with nitric oxide (NO) signaling, potentially promoting blood clots. This study identifies specific heparin structures that react with NO, impacting its antiplatelet effects.
Area of Science:
- Biochemistry
- Pharmacology
- Hematology
Background:
- Heparin is a widely used anticoagulant, but paradoxically can induce a prothrombotic state via platelet activation.
- Nitric oxide (NO) is crucial for antiplatelet and vasorelaxant functions, and its donors are used therapeutically.
Purpose of the Study:
- To investigate how heparin interacts with and potentially neutralizes nitric oxide (NO).
- To identify the specific structural features of heparin responsible for this interaction.
Main Methods:
- Spectroscopic analysis (UV/Vis, Griess assay) to detect NO species.
- Comparison of six different heparin disaccharides to pinpoint functional group involvement.
- Mass spectrometry (MS, MS/MS) to analyze chemical modifications of heparin structures.
Main Results:
- Heparin dose-dependently eliminated acidified nitric oxide (NOx) species, reversing the antiplatelet effect of S-nitroso-glutathione (SNO-Glu).
- Only N-sulfated heparin disaccharides (I-S and II-S) showed significant interaction with NOx.
- Mass spectrometry confirmed modification of these disaccharides, involving the C2-sulfamino group and facilitated by the 6-sulfato substituent.
Conclusions:
- Heparin impairs the antiplatelet properties of nitric oxide by reacting with nitrosating species.
- Specific structural features of heparin, particularly N-sulfation, are critical for this interaction.
- Heparin-like glycosaminoglycans may modulate the bioactivity of endogenous nitric oxide in vivo.
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