title: Low-grade systemic inflammation causes endothelial dysfunction in patients with Hashimoto's thyroiditis.
abstract: OBJECTIVE
  The objective of this study was to assess whether low-grade systemic inflammation might contribute to the pathogenesis of endothelial dysfunction in patients with subclinical hypothyroidism (sHT) and autoimmune thyroiditis.
  
  
  BACKGROUND
  sHT patients are characterized by peripheral endothelial dysfunction and low-grade inflammation.
  
  
  METHODS
  In 53 sHT and 45 healthy subjects, we studied the forearm blood flow (strain-gauge plethysmography) response to intrabrachial acetylcholine (Ach) (0.15-15 microg/min.dl) with and without local vascular COX inhibition by intrabrachial indomethacin (50 microg/min.dl) or nitric oxide synthase blockade by N-mono methyl arginine (L-NMMA) (100 microg/min.dl) or the antioxidant vitamin C (8 mg/min.dl). The protocol was repeated 2 h after systemic nonselective COX inhibition (100 mg indomethacin) or selective COX-2 blockade (200 mg celecoxib) oral administrations.
  
  
  RESULTS
  sHT patients showed higher C-reactive protein and IL-6 values. In controls, vasodilation to Ach was blunted by L-NMMA and unchanged by vitamin C. In contrast, in sHT, the response to Ach, reduced in comparison with controls, was resistant to L-NMMA and normalized by vitamin C. In these patients, systemic but not local indomethacin normalized vasodilation to Ach and the inhibition of L-NMMA on Ach. Similar results were obtained with celecoxib. When retested after indomethacin administration, vitamin C no longer succeeded in improving vasodilation to Ach in sHT patients. Response to sodium nitroprusside was unchanged by indomethacin or celecoxib.
  
  
  CONCLUSIONS
  In sHT patients, low-grade chronic inflammation causes endothelial dysfunction and impaired nitric oxide availability by a COX-2-dependent pathway leading to increased production of oxidative stress.
authors.affiliation: Department of Internal Medicine, University of Pisa, Via Roma, 67-56100 Pisa, Italy. s.taddei@med.unipi.it
authors.forename: Stefano
authors.initials: S
authors.lastname: Taddei
authors.forename: Nadia
authors.initials: N
authors.lastname: Caraccio
authors.forename: Agostino
authors.initials: A
authors.lastname: Virdis
authors.forename: Angela
authors.initials: A
authors.lastname: Dardano
authors.forename: Daniele
authors.initials: D
authors.lastname: Versari
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Ghiadoni
authors.forename: Ele
authors.initials: E
authors.lastname: Ferrannini
authors.forename: Antonio
authors.initials: A
authors.lastname: Salvetti
authors.forename: Fabio
authors.initials: F
authors.lastname: Monzani
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000465:Algorithms; D001205:Ascorbic Acid / Q000494:pharmacology; D000068579:Celecoxib; D051546:Cyclooxygenase 2; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D050031:Hashimoto Disease / Q000150:complications*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000150:complications*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009569:Nitric Oxide / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology; D011720:Pyrazoles / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D014652:Vascular Diseases / Q000209:etiology*; D014657:Vasculitis / Q000150:complications; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D008565:Membrane Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D009599:Nitroprusside; D009569:Nitric Oxide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000068579:Celecoxib; D000109:Acetylcholine; D001205:Ascorbic Acid; D007213:Indomethacin