title: NO-mediated anticontractile effect of the endothelium is abolished in coronary arteries of adult rats with antenatal/early postnatal hypothyroidism.
abstract: BACKGROUND
  Thyroid hormones are essential for proper development of many systems and organs, including circulatory system. Thyroid deficiency during pregnancy may affect the cardiovascular function in children early on and later in adulthood. However, long-term effects of early thyroid deficiency are poorly understood. We hypothesized that antenatal/early postnatal hypothyroidism will influence anticontractile effect of NO in coronary arteries of adult rats.
  
  
  METHODS
  To model antenatal/early postnatal hypothyroidism dams were treated with 6-propyl-2-thiouracil (PTU) in drinking water (0.0007%, w/v) from the first day of pregnancy till 2 weeks after delivery. Control females were supplied with pure water. Their male offspring was grown up till the age of 10-12 weeks. Systolic blood pressure was measured using tail cuff method. Septal coronary arteries were isolated and studied in wire myograph. Blood serum thyroid hormones concentrations (ELISA) and NO metabolites level (Griess method) were evaluated.
  
  
  RESULTS
  At the age of 10-12 weeks thyroid hormones, TSH concentrations, NO metabolites and systolic blood pressure level didn't differ between groups. Arterial responses to acetylcholine and exogenous NO-donor DEA/NO were similar in control and PTU groups. Along with that, in control rats endothelium denudation strongly potentiated basal tone of arteries and their contractile responses to thromboxane A2 receptor agonist U46619. The effects of endothelium denudation were absent in PTU rats indicating that anticontractile effect of endothelium is abolished in their arteries. Further, NO-synthase inhibitor L-NNA (100 μM) caused significant elevation of basal tone and increased U46619-induced contraction of endothelium-intact arteries only in control rats, while had no effect in PTU group.
  
  
  CONCLUSIONS
  Our data demonstrate that NO-mediated anticontractile effect of endothelium is eliminated in coronary arteries of adult rats, which suffered from antenatal/early postnatal hypothyroidism. Therefore, maternal thyroid hormones deficiency may have detrimental consequences in adult offspring including coronary circulation pathologies, despite normal blood levels of thyroid hormones.
authors.affiliation: Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1/12, 119234, Moscow, Russia; Institute for Biomedical Problems, Russian Academy of Sciences, Khoroshevskoe shosse 76A, 123007, Moscow, Russia; Department of Physiology, Russian National Research Medical University, Ostrovitianova str. 1, 117997, Moscow, Russia. Electronic address: dina.gaynullina@gmail.com.
authors.forename: Dina K
authors.initials: DK
authors.lastname: Gaynullina
authors.affiliation: Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1/12, 119234, Moscow, Russia; Institute for Biomedical Problems, Russian Academy of Sciences, Khoroshevskoe shosse 76A, 123007, Moscow, Russia.
authors.forename: Svetlana I
authors.initials: SI
authors.lastname: Sofronova
authors.affiliation: Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1/12, 119234, Moscow, Russia.
authors.forename: Ekaterina K
authors.initials: EK
authors.lastname: Selivanova
authors.affiliation: Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1/12, 119234, Moscow, Russia; Institute for Biomedical Problems, Russian Academy of Sciences, Khoroshevskoe shosse 76A, 123007, Moscow, Russia.
authors.forename: Anastasia A
authors.initials: AA
authors.lastname: Shvetsova
authors.affiliation: Institute for Biomedical Problems, Russian Academy of Sciences, Khoroshevskoe shosse 76A, 123007, Moscow, Russia.
authors.forename: Anna A
authors.initials: AA
authors.lastname: Borzykh
authors.affiliation: Institute for Biomedical Problems, Russian Academy of Sciences, Khoroshevskoe shosse 76A, 123007, Moscow, Russia.
authors.forename: Anna P
authors.initials: AP
authors.lastname: Sharova
authors.affiliation: Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1/12, 119234, Moscow, Russia; Institute for Biomedical Problems, Russian Academy of Sciences, Khoroshevskoe shosse 76A, 123007, Moscow, Russia.
authors.forename: Daria S
authors.initials: DS
authors.lastname: Kostyunina
authors.affiliation: Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1/12, 119234, Moscow, Russia; Institute for Biomedical Problems, Russian Academy of Sciences, Khoroshevskoe shosse 76A, 123007, Moscow, Russia.
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Martyanov
authors.affiliation: Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1/12, 119234, Moscow, Russia; Institute for Biomedical Problems, Russian Academy of Sciences, Khoroshevskoe shosse 76A, 123007, Moscow, Russia.
authors.forename: Olga S
authors.initials: OS
authors.lastname: Tarasova
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000503:physiopathology*; D004048:Diethylamines / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D007037:Hypothyroidism / Q000503:physiopathology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D017208:Rats, Wistar
chemical_list: D004048:Diethylamines; D020030:Nitric Oxide Donors; D019335:Nitroarginine; D009569:Nitric Oxide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C087229:diethylamine dinitric oxide adduct; D019001:Nitric Oxide Synthase
keywords: 6-propyl-2-thiouracil; Coronary arteries; Development; Endothelium; Nitric oxide; Thyroid hormones