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(Circulation. 2002;106:170.)
© 2002 American Heart Association, Inc.

Editorial

Mechanisms Underlying Nitroglycerin-Induced Superoxide Production in Platelets

Some Insight, More Questions

Thomas Münzel, MD; Alexander Mülsch, MD; Andrej Kleschyov, PhD

From University Hospital Eppendorf, Division of Cardiology, Hamburg (T.M., A.L.K.), and the Johann Wolfgang Goethe University, Department of Physiology, Frankfurt (A.M.), Germany.

Correspondence to Thomas Münzel, MD, Abteilung für Kardiologie, Universitäts-Krankenhaus Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany. E-mail muenzel@uke.uni-hamburg.de

Key Words: Editorials • nitroglycerin • ptelets • nitric oxide synthase • antioxidants

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Nitroglycerin (NTG) has been the foremost anti-ischemic agent used in clinical medicine for more than a century. NTG is a potent vasodilator of veins, arterial conductance vessels, and collaterals that has minimal effects on arteriolar tone. At the cellular level, NTG is biotransformed by a still unknown enzymatic process in endothelial cells, smooth muscle, and to some extent platelets, causing it to release the vasodilator and anti-aggregatory principle nitric oxide. The 2 major drawbacks of nitrate therapy that have been shown to be important are the rapid development of nitrate tolerance¹ and endothelial dysfunction^2,3 within several days of prolonged NTG treatment. There is a growing body of evidence that both NTG-induced side effects may be at least in part secondary to NTG-stimulated production of oxygen-derived free radicals within vascular tissue.^4–6 Increased oxidative stress correlates positively with increased cardiovascular event rates,⁷ which may, at least in part, explain why NTG-therapy either failed to improve or worsened the prognosis in patients with acute myocardial infarction and chronic ischemic heart disease, respectively.

See p 208

For years, investigators have been debating whether NTG has significant antiplatelet activity. Several studies demonstrated that inhibition of platelet aggregation by NTG occurs in suprapharmacological dosis, denying any clinically relevant antiplatelet activity. Whether or not NTG inhibits platelet aggregation clearly depends on the chosen experimental conditions. For example, in washed platelets, the lowest effective concentrations of NTG that inhibit platelet aggregation are consistently in the µmol/L range and are therefore in concentrations that are 1000 times higher than . . . [Full Text of this Article]

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