title: Nitroglycerin use in myocardial infarction patients.
abstract: Acute myocardial infarction (MI) and its sequelae are leading causes of morbidity and mortality worldwide. Nitroglycerin (glyceryl trinitrate [GTN]) remains a first-line treatment for angina pectoris and acute MI. Nitroglycerin achieves its benefit by giving rise to nitric oxide (NO), which causes vasodilation and increases blood flow to the myocardium. However, continuous delivery of GTN results in tolerance, limiting the use of this drug. Nitroglycerin tolerance is caused, at least in part, by inactivation of aldehyde dehydrogenase 2 (ALDH2), an enzyme that converts GTN to the vasodilator, NO. We recently found that in a MI model in animals, in addition to GTN's effect on the vasculature, sustained treatment negatively affected cardiomyocyte viability following ischemia, thus resulting in increased infarct size. Coadministration of Alda-1, an activator of ALDH2, with GTN improves metabolism of reactive aldehyde adducts and prevents the GTN-induced increase in cardiac dysfunction following MI. In this review, we describe the molecular mechanisms associated with the benefits and risks of GTN administration in MI.
authors: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305-5174, USA.
authors: Julio C B
authors: JC
authors: Ferreira
authors: Daria
authors: D
authors: Mochly-Rosen
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000502:physiology; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004361:Drug Tolerance / Q000502:physiology*; D006801:Humans; D023421:Models, Animal; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D005996:Nitroglycerin / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D014665:Vasodilator Agents; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D005996:Nitroglycerin