title: Iron sucrose augments homocysteine-induced endothelial dysfunction in normal subjects.
abstract: Intravenous iron is commonly used in conjunction with erythropoietic agents to treat anemia in patients with chronic kidney disease. Iron has been proposed to promote oxidative stress and endothelial dysfunction in vascular tissues. We studied the acute effects of intravenous iron sucrose on homocysteine-induced endothelial dysfunction in the brachial artery of normal human subjects. In all, 40 healthy subjects received intravenous iron sucrose 100 mg or placebo over 30 min immediately before ingestion of 100 mg/kg of oral methionine in a double-blind, randomized study. Flow- and nitroglycerin-mediated dilation in the brachial artery, serum markers of iron stores, and homocysteine and nitrotyrosine levels were measured before and after study drug administration. Intravenous iron significantly increased transferrin saturation and non-transferrin-bound iron (NTBI) when compared with placebo. Flow-mediated dilation significantly decreased from baseline 1 h after administration of iron sucrose when compared with placebo (from 6.66+/-0.47 to 1.93+/-0.35% after iron sucrose vs from 6.00+/-0.40 to 5.61+/-0.46% after placebo, P<0.001), but did not differ between groups at 4 h (1.10+/-0.39 vs 1.33+/-0.51%). Nitroglycerin-mediated vasodilation, and homocysteine and 3-nitrotyrosine levels did not differ after administration of iron sucrose and placebo. Intravenous administration of iron sucrose in the setting of transient hyperhomocysteinemia induced by methionine ingestion significantly increased transferrin saturation and plasma levels of NTBI and significantly attenuated flow-mediated dilation in the brachial artery when compared with placebo. This potential mechanistic link between intravenous iron and endothelial dysfunction warrants further study of cardiovascular effects of intravenous iron in anemic chronic kidney disease populations.
authors.affiliation: Department of Medicine, Yale University School of Medicine, New Haven, Conneticut 06510, USA.
authors.forename: H
authors.initials: H
authors.lastname: Zheng
authors.forename: X
authors.initials: X
authors.lastname: Huang
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.forename: S D
authors.initials: SD
authors.lastname: Katz
mesh_terms: D000328:Adult; D018798:Anemia, Iron-Deficiency / Q000188:drug therapy; D001916:Brachial Artery / Q000187:drug effects / Q000502:physiology; D002318:Cardiovascular Diseases / Q000503:physiopathology; D002614:Chelating Agents / Q000494:pharmacology; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D000077605:Ferric Oxide, Saccharated; D005293:Ferritins / Q000097:blood; D005937:Glucaric Acid; D006710:Homocysteine / Q000097:blood / Q000502:physiology*; D006801:Humans; D007501:Iron / Q000097:blood / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use; D008297:Male; D008715:Methionine / Q000494:pharmacology / Q000502:physiology; D005996:Nitroglycerin / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology; D011929:Razoxane / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D012307:Risk Factors; D014168:Transferrin / Q000032:analysis; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood; D014664:Vasodilation / Q000187:drug effects
chemical_list: D002614:Chelating Agents; D005290:Ferric Compounds; D014168:Transferrin; D006710:Homocysteine; C002744:3-nitrotyrosine; D014443:Tyrosine; D011929:Razoxane; D005293:Ferritins; D008715:Methionine; D007501:Iron; D000077605:Ferric Oxide, Saccharated; D005996:Nitroglycerin; D005937:Glucaric Acid