title: Antioxidant is a useful supportive agent for the treatment of coronary vasospasm with endothelial dysfunction in pig.
abstract: OBJECTIVE
  Recently, many antioxidants have been tested in cardiovascular disease. The effect of antioxidants on alleviation of coronary vasospasm, however, remains unclear. We investigated whether chronic administration of ascorbic acid and glutathione prevents coronary vasospasm in pigs.
  
  
  METHODS
  Balloon-induced endothelial injury in the left anterior descending coronary artery was performed every 2 weeks until 6 weeks (0, 2, 4, 6 weeks). Ten micrograms per kilogram serotonin-induced vasoconstriction was assessed before each endothelial injury and at eighth week by coronary angiography.
  
  
  RESULTS
  In endothelial injury without antioxidant group (ED group, n=12), serotonin-induced left anterior descending coronary artery vasoconstriction was augmented from 7+/-4% (0 week) to 88+/-8% (8th week, P<0.01) with electrocardiogram-ST elevation, and an increase of cyclooxygenase-2 expression and a decrease of endothelial nitric oxide synthase expression was observed at the spasm portion removed from the endothelial denuded site. In the endothelial injury group with oral administration of ascorbic acid 3 g/day and glutathione 1 g/day after the first endothelial injury (ASC+GSH group, n=12), serotonin-induced vasoconstriction was suppressed (8th week, 60+/-6%, P<0.01 vs. ED group) and endothelial nitric oxide synthase expression was fairly well maintained. Intimal thickening was observed at the left anterior descending artery spasm portion in the endothelial injury without antioxidant group but not at the corresponding portion in the ASC+GSH group.
  
  
  CONCLUSIONS
  Antioxidant therapy was partially effective to prevent coronary vasospasm, whereas intimal thickening after endothelial injury was nearly restored. From these results, chronic antioxidant therapy may well be a useful supportive therapy for the treatment of coronary vasospasm, although it has limited availability despite amelioration of endothelial dysfunction.
authors.affiliation: First Department of Internal Medicine, Fukushima Medical University, Fukushima, Japan.
authors.forename: Futoshi
authors.initials: F
authors.lastname: Onogi
authors.forename: Shu-ichi
authors.initials: S
authors.lastname: Saitoh
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Aikawa
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Ishibashi
authors.forename: Yukio
authors.initials: Y
authors.lastname: Maruyama
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000378:metabolism; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000097:blood; D003329:Coronary Vasospasm / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D005978:Glutathione / Q000008:administration & dosage / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D013552:Swine; D017539:Tunica Intima / Q000473:pathology
chemical_list: D000975:Antioxidants; D052250:Nitric Oxide Synthase Type III; D051546:Cyclooxygenase 2; D005978:Glutathione; D001205:Ascorbic Acid