title: Propylthiouracil, independent of its antithyroid effect, produces endothelium-dependent vasodilatation through induction of nitric oxide bioactivity.
abstract: OBJECTIVE
  Propylthiouracil (PTU), independent of its antithyroid effect, is recently found to have a potent antiatherosclerotic effect. The aim of this study is to investigate whether PTU has a beneficial effect on endothelial function.
  
  
  RESULTS
  Ninety patients with a history of hyperthyroidism receiving either PTU (n=45) or methimazole (MMI) (n=45) during the euthyroid status were enrolled in this study. Brachial artery endothelium-dependent (flow-mediated dilatation [FMD]) and endothelium-independent (nitroglycerin-mediated dilatation) responses were assessed by high-resolution ultrasound image. Data for these two groups were compared with those of 41 healthy control subjects. The FMD values were significantly increased in patients maintained on PTU versus those in the MMI and control groups (9.3+/-4.4%, 3.4+/-2.5%, and 3.6+/-3.4%, respectively; P<0.01). Nitroglycerin-mediated dilatation had no significant difference between the PTU, MMI, and control groups (17.4+/-7.5%, 15.9+/-6.1%, and 17.5+/-6.8%, respectively; P=0.455). On multivariate analysis, no significant relationship was found between the FMD and thyroid hormone index levels. To further elucidate whether PTU has a direct effect on endothelial function, the effect of PTU on isolated segments of Sprague-Dawley rat aorta was studied. Vasodilatation induced by PTU was endothelium-dependent and could be blocked by pretreatment with nitric oxide (NO) inhibitors. PTU also increased NO formation in aortic segments.
  
  
  CONCLUSIONS
  This study demonstrated that PTU produced endothelium-dependent vasodilatation through thyroid-independent and NO-mediated mechanisms that may contribute to its beneficial effect on atherosclerosis.
authors.affiliation: First Cardiovascular Division, Department of Cardiology, Chang Gung Memorial Hospital, Fu-Shin Road no. 5, Kwei-Shan, Tao-Yuan 333, Taiwan. Electronic address: wjchen@adm.cgmh.org.tw.
authors.forename: Wei-Jan
authors.initials: WJ
authors.lastname: Chen
authors.affiliation: First Cardiovascular Division, Department of Cardiology, Chang Gung Memorial Hospital, Fu-Shin Road no. 5, Kwei-Shan, Tao-Yuan 333, Taiwan.
authors.forename: Wan-Jing
authors.initials: WJ
authors.lastname: Ho
authors.affiliation: Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Tao-Yuan, Taiwan.
authors.forename: Gwo-Jyh
authors.initials: GJ
authors.lastname: Chang
authors.affiliation: Department of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
authors.forename: Szu-Tah
authors.initials: ST
authors.lastname: Chen
authors.affiliation: Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Tao-Yuan, Taiwan.
authors.forename: Jong-Hwei S
authors.initials: JS
authors.lastname: Pang
authors.affiliation: Department of Physiology, Chang Gung University College of Medicine, Tao-Yuan, Taiwan.
authors.forename: Shih-Hsuan
authors.initials: SH
authors.lastname: Chou
authors.affiliation: Department of Public Health & Center of Biostatistics, Chang Gung University College of Medicine, Tao-Yuan, Taiwan.
authors.forename: Pei-Kwei
authors.initials: PK
authors.lastname: Tsay
authors.affiliation: First Cardiovascular Division, Department of Cardiology, Chang Gung Memorial Hospital, Fu-Shin Road no. 5, Kwei-Shan, Tao-Yuan 333, Taiwan.
authors.forename: Chi-Tai
authors.initials: CT
authors.lastname: Kuo
mesh_terms: D000328:Adult; D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006980:Hyperthyroidism / Q000188:drug therapy*; D008297:Male; D008713:Methimazole / Q000494:pharmacology; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D011441:Propylthiouracil / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D013956:Antithyroid Agents; D009569:Nitric Oxide; D008713:Methimazole; D011441:Propylthiouracil