title: Organic nitrates and nitrate resistance in diabetes: the role of vascular dysfunction and oxidative stress with emphasis on antioxidant properties of pentaerithrityl tetranitrate.
abstract: Organic nitrates represent a class of drugs which are clinically used for treatment of ischemic symptoms of angina as well as for congestive heart failure based on the idea to overcome the impaired NO bioavailability by "NO" replacement therapy. The present paper is focused on parallels between diabetes mellitus and nitrate tolerance, and aims to discuss the mechanisms underlying nitrate resistance in the setting of diabetes. Since oxidative stress was identified as an important factor in the development of tolerance to organic nitrates, but also represents a hallmark of diabetic complications, this may represent a common principle for both disorders where therapeutic intervention should start. This paper examines the evidence supporting the hypothesis that pentaerithrityl tetranitrate may represent a nitrate for treatment of ischemia in diabetic patients. This evidence is based on the considerations of parallels between diabetes mellitus and nitrate tolerance as well as on preliminary data from experimental diabetes studies.
authors.affiliation: The 2nd Medical Clinic, Laboratory for Molecular Cardiology, University Medical Center, Johannes Gutenberg University of Mainz, 55101 Mainz, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Oelze
authors.forename: Swenja
authors.initials: S
authors.lastname: Schuhmacher
authors.forename: Andreas
authors.initials: A
authors.lastname: Daiber
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000503:physiopathology; D004351:Drug Resistance; D004730:Endothelium, Vascular / Q000503:physiopathology; D006801:Humans; D009566:Nitrates / Q000378:metabolism / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D010417:Pentaerythritol Tetranitrate / Q000627:therapeutic use*; D014665:Vasodilator Agents
chemical_list: D000975:Antioxidants; D009566:Nitrates; D014665:Vasodilator Agents; D010417:Pentaerythritol Tetranitrate; D009569:Nitric Oxide