title: Aging aggravates nitrate-mediated ROS/RNS changes.
abstract: Nitrates are the most frequently prescribed and utilized drugs worldwide. The elderly are a major population receiving nitrate therapy. Both nitrates and aging can increase in vivo reactive oxygen species (ROS) and reactive nitrogen species (RNS). To date, the effects of aging upon nitrate-induced ROS/RNS alteration are unknown. The present study tested the effects of aging upon nitrate-induced ROS/RNS alteration in vivo. 32 adults and 43 elderly unstable angina (UA) patients were subjected to 48 hours of isosorbide dinitrate intravenous injection (50  μg/minutes) in this clinical study. Blood samples were obtained at baseline and conclusion. Outcome measures of oxidative stress included plasma malondialdehyde (MDA), myeloperoxidase (MPO), and reduced glutathione (GSH). Plasma concentrations of NOx and nitrotyrosine served as markers of RNS. Because of the significant differences in basic clinical characters between adults and the elderly, we designed an additional experiment determining ROS/RNS stress in rat cardiac tissue. Additionally, rat thoracic aortic NOS activity served as a marker indicating endothelial function. Our study demonstrated that nitrate therapy significantly increased in vivo ROS/RNS stress in the elderly compared to adult patients, confirmed by animal data. Decreased NOS activity was observed in old rats. Taken together, the present study's data suggests a synergism between nitrate treatment and the aging process.
authors.affiliation: Department of Cardiology, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Disease, Beijing 100029, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Fan
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Chong Qing Medical University, Chong Qing, China.
authors.forename: Lifen
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Disease, Beijing 100029, China.
authors.forename: Shujuan
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Department of Cardiology, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Disease, Beijing 100029, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Wayne Bond
authors.initials: WB
authors.lastname: Lau
authors.affiliation: Heart Center, Beijing Chaoyang Hospital-Affiliate of Beijing Capital Medical University, 8 Gongtinan Road, Beijing 100020, China.
authors.forename: Le Feng
authors.initials: le F
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Disease, Beijing 100029, China.
authors.forename: Jing Hua
authors.initials: JH
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging; D000789:Angina, Unstable / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000097:blood; D006801:Humans; D007548:Isosorbide Dinitrate / Q000627:therapeutic use*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009195:Peroxidase / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
chemical_list: D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D005978:Glutathione; D007548:Isosorbide Dinitrate