Urinary Nitrotyrosine Content as a Marker of Peroxynitrite-induced Tolerance to Organic Nitrates

Abstract

Background: Anti-ischemic therapy with nitrovasodilators as NO-donors is complicated by the induction of tolerance. When nitrovasodilators are metabolized to release NO there is a considerable coproduction of oxygen-derived radicals leading to a diminished cyclic GMP production and to impaired vasomotory responses. We analyzed in vivo the glyceroltrinitrate- induced generation of strong oxidative/nitrating compounds contributing to development of tolerance.