title: Antioxidants improve vascular function in children conceived by assisted reproductive technologies: A randomized double-blind placebo-controlled trial.
abstract: OBJECTIVE
  Children conceived by assisted reproductive technology (ART) display vascular dysfunction. Its underlying mechanism, potential reversibility and long-term consequences for cardiovascular risk are unknown. In mice, ART induces arterial hypertension and shortens the life span. These problems are related to decreased vascular endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) synthesis. The aim of this study was to determine whether ART-induced vascular dysfunction in humans is related to a similar mechanism and potentially reversible. To this end we tested whether antioxidants improve endothelial function by scavenging free radicals and increasing NO bioavailability.
  
  
  RESULTS
  In this prospective double-blind placebo controlled study in 21 ART and 21 control children we assessed the effects of a four-week oral supplementation with antioxidant vitamins C (1 g) and E (400 IU) or placebo (allocation ratio 2:1) on flow-mediated vasodilation (FMD) of the brachial artery and pulmonary artery pressure (echocardiography) during high-altitude exposure (3454 m), a manoeuver known to facilitate the detection of pulmonary vascular dysfunction and to decrease NO bioavailability by stimulating oxidative stress. Antioxidant supplementation significantly increased plasma NO measured by ozone-based chemiluminescence (from 21.7 ± 7.9 to 26.9 ± 7.6 µM, p = 0.04) and FMD (from 7.0 ± 2.1 to 8.7 ± 2.0%, p = 0.004) and attenuated altitude-induced pulmonary hypertension (from 33 ± 8 to 28 ± 6 mm Hg, p = 0.028) in ART children, whereas it had no detectable effect in control children.
  
  
  CONCLUSIONS
  Antioxidant administration to ART children improved NO bioavailability and vascular responsiveness in the systemic and pulmonary circulation. Collectively, these findings indicate that in young individuals ART-induced vascular dysfunction is subject to redox regulation and reversible.
authors.affiliation: Department of Cardiology and Clinical Research, Inselspital, University Hospital, Bern, Switzerland stefano.rimoldi@insel.ch.
authors.forename: Stefano F
authors.initials: SF
authors.lastname: Rimoldi
authors.affiliation: Department of Cardiology and Clinical Research, Inselspital, University Hospital, Bern, Switzerland Department of Internal Medicine, Centre Hospitalieruniversitaire Vaudois (CHUV), Lausanne, Switzerland.
authors.forename: Claudio
authors.initials: C
authors.lastname: Sartori
authors.affiliation: Department of Cardiology and Clinical Research, Inselspital, University Hospital, Bern, Switzerland.
authors.forename: Emrush
authors.initials: E
authors.lastname: Rexhaj
authors.affiliation: Neurovascular Research Laboratory, University of South Wales, UK.
authors.forename: Damian M
authors.initials: DM
authors.lastname: Bailey
authors.affiliation: Department of Cardiology and Clinical Research, Inselspital, University Hospital, Bern, Switzerland.
authors.forename: Stefano F
authors.initials: SF
authors.lastname: de Marchi
authors.affiliation: Centre for Clinical and Population Sciences, Queen's University, Northern Ireland.
authors.forename: Jane
authors.initials: J
authors.lastname: McEneny
authors.affiliation: Department of Cardiology and Clinical Research, Inselspital, University Hospital, Bern, Switzerland.
authors.forename: Robert von
authors.initials: Rv
authors.lastname: Arx
authors.affiliation: Department of Cardiology and Clinical Research, Inselspital, University Hospital, Bern, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Cerny
authors.affiliation: Department of Internal Medicine, Delémont, Switzerland.
authors.forename: Hervé
authors.initials: H
authors.lastname: Duplain
authors.affiliation: Centre de Procréation Médicalement Assistée, Lausanne, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Germond
authors.affiliation: Department of Cardiology and Clinical Research, Inselspital, University Hospital, Bern, Switzerland.
authors.forename: Yves
authors.initials: Y
authors.lastname: Allemann
authors.affiliation: Department of Cardiology and Clinical Research, Inselspital, University Hospital, Bern, Switzerland Facultad de Ciencias, Departamento de Biología, Universidad de Tarapacá, Chile.
authors.forename: Urs
authors.initials: U
authors.lastname: Scherrer
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000531:Altitude; D000975:Antioxidants / Q000627:therapeutic use*; D062186:Arterial Pressure / Q000187:drug effects; D001205:Ascorbic Acid / Q000627:therapeutic use*; D001916:Brachial Artery / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002648:Child; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011446:Prospective Studies; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D020127:Recovery of Function; D027724:Reproductive Techniques, Assisted / Q000009:adverse effects*; D013557:Switzerland; D013997:Time Factors; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects; D014810:Vitamin E / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D014810:Vitamin E; D009569:Nitric Oxide; D001205:Ascorbic Acid
keywords: Endothelial dysfunction; in vitro fertilization; nitric oxide; vitamin