title: Long-term isosorbide mononitrate treatment impairs endothelial function in patients with coronary artery disease.
abstract: BACKGROUND
  Sustained use of nitrates is associated with adverse effects on vascular function by increasing oxidative stress. It remains unclear whether oxidative stress impairs endothelial function in patients with coronary artery disease (CAD) during long-term oral use of nitrates. The purpose of this study was to evaluate the effects of long-term isosorbide mononitrate (ISMN) treatment on oxidative stress and endothelial function in patients with CAD.
  
  
  METHODS
  In this prospective, double-blinded, placebo-controlled, randomized, single-center study, 60 patients were assigned to treatment with ISMN 20 mg retarded release orally twice per day (ISMN group, n=30) or placebo (control group, n=30) for 1 year. The primary endpoint was the change in brachial artery endothelium-dependent dilation [flow-mediated dilation (FMD)] from baseline to follow-up. Furthermore, serum superoxide dismutase, malondialdehyde, and hypersensitive C-reactive protein levels were also measured at baseline and follow-up.
  
  
  RESULTS
  The FMD decreased significantly (from 5.97±2.88 to 5.33±2.56%) in the ISMN group, whereas it increased from 6.27±3.23 to 6.96±2.84% in the control group after treatment for 1 year. There was a significant difference in the changes in FMD when the two groups were compared (-0.64±1.83 vs. 0.69±1.77%, P=0.006). There were no significant changes in serum superoxide dismutase, malondialdehyde, and hypersensitive C-reactive protein levels in the two groups.
  
  
  CONCLUSIONS
  Long-term ISMN treatment may impair endothelial function in patients with CAD.
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Lai
authors.forename: Bifeng
authors.initials: B
authors.lastname: Wu
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Shang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000284:Administration, Oral; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001916:Brachial Artery / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002097:C-Reactive Protein / Q000378:metabolism; D002681:China; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D011446:Prospective Studies; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D015415:Biomarkers; D014665:Vasodilator Agents; D008315:Malondialdehyde; D002097:C-Reactive Protein; D013482:Superoxide Dismutase; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate