Formation of Reactive Oxygen Species in Various Vascular Cells During Glyceryltrinitrate Metabolism

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Abstract
Background: Anti-ischemic therapy with organic nitrates as nitric oxide (NO) donors is complicated by the induction of tolerance. When nitrates are metabolized to release NO, there is a considerable coproduction of reactive oxygen species (superoxide radical and per oxynitrite) in vessels leading to inactivation of NO, to diminished cyclic quanosine mono phosphate production in smooth muscle cells (SMC), to impaired vasomotor responses to the endothelium-derived relaxation factor (EDRF), and to formation of nitrotyrosine as a marker of glyceryltrinitrate (GTN)-induced formation of peroxynitrite. The aim of the study was to analyze in vitro the formation of superoxide radicals and of peroxynitrite in GTN-treated endothelial and smooth muscle cells and in washed ex vivo platelets using electron spin resonance and spin-trapping techniques.