title: Nitric oxide mediates abnormal responsiveness of thyroid arteries in methimazole-treated patients.
abstract: OBJECTIVE
  We studied the intervention of nitric oxide (NO), prostacyclin and endothelium-derived hyperpolarizing factor (EDHF) in mediating responses to acetylcholine in thyroid arteries from euthyroid and methimazole-treated (MT) patients.
  
  
  METHODS
  Branches of the superior thyroid artery were obtained from 19 euthyroid patients and 17 MT patients (euthyroid at the time of surgery) undergoing total thyroidectomy or hemithyroidectomy. Artery rings were suspended in organ baths for isometric recording of tension.
  
  
  CONCLUSIONS
  Acetylcholine caused endothelium-dependent relaxation of greater magnitude in arteries from MT patients (pD(2) (-log EC(50)) values were 7.68 +/- 0.19 in euthyroid and 8.17 +/- 0.26 in MT patients, P < 0.05). The relaxation was unaffected by indomethacin and was partially reduced by the NO-synthase inhibitor NG-monomethyl-L-arginine (L-NMMA). This reduction was higher in arteries from MT patients (50 +/- 6%) as compared with euthyroid patients (36 +/- 6%) (P < 0.05). Inhibition of K(+) channels using apamin combined with charybdotoxin or high K(+) solution abolished the relaxation resistance to L-NMMA and indomethacin. The maximal contraction response to noradrenaline (as a percentage of the response to 100 mM KCl) was lower in MT than in euthyroid patients (57 +/- 10 and 96 +/- 8 respectively, P < 0.05). The hyporesponsiveness to noradrenaline in arteries from MT patients was corrected by L-NMMA. The results indicate that: (i) thyroid arteries from MT patients show an increased relaxation response to acethylcholine and a decreased contraction response to noradrenaline due to overproduction of NO; (ii) EDHF plays a prominent role in acetylcholine-induced relaxation through activation of Ca(2+)-activated K(+) channels; (iii) the abnormal endothelium-dependent responses in arteries from MT patients are not corrected by medical treatment.
authors.affiliation: Department of Surgery, Hospital Clínico Research Unit, University of Valencia, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Ortega
authors.forename: José M
authors.initials: JM
authors.lastname: Vila
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Mauricio
authors.forename: Gloria
authors.initials: G
authors.lastname: Segarra
authors.forename: Pascual
authors.initials: P
authors.lastname: Medina
authors.forename: Juan B
authors.initials: JB
authors.lastname: Martínez-León
authors.forename: Salvador
authors.initials: S
authors.lastname: Lluch
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D013956:Antithyroid Agents / Q000627:therapeutic use*; D001030:Apamin / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology*; D001685:Biological Factors / Q000502:physiology; D002118:Calcium / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D006980:Hyperthyroidism / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008713:Methimazole / Q000627:therapeutic use*; D008875:Middle Aged; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D013961:Thyroid Gland / Q000098:blood supply*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D013956:Antithyroid Agents; D001685:Biological Factors; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C067410:endothelium-dependent hyperpolarization factor; D018999:Charybdotoxin; D001030:Apamin; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D008713:Methimazole; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine