Propylthiouracil, independent of its antithyroid effect, produces endothelium-dependent vasodilatation through induction of nitric oxide bioactivity.
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.
Chen
Wei-Jan
WJ
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.
Ho
Wan-Jing
WJ
First Cardiovascular Division, Department of Cardiology, Chang Gung Memorial Hospital, Fu-Shin Road no. 5, Kwei-Shan, Tao-Yuan 333, Taiwan.
Chang
Gwo-Jyh
GJ
Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Tao-Yuan, Taiwan.
Chen
Szu-Tah
ST
Department of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
Pang
Jong-Hwei S
JS
Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Tao-Yuan, Taiwan.
Chou
Shih-Hsuan
SH
Department of Physiology, Chang Gung University College of Medicine, Tao-Yuan, Taiwan.
Tsay
Pei-Kwei
PK
Department of Public Health & Center of Biostatistics, Chang Gung University College of Medicine, Tao-Yuan, Taiwan.
Kuo
Chi-Tai
CT
First Cardiovascular Division, Department of Cardiology, Chang Gung Memorial Hospital, Fu-Shin Road no. 5, Kwei-Shan, Tao-Yuan 333, Taiwan.
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*
D013956:Antithyroid Agents; D009569:Nitric Oxide; D008713:Methimazole; D011441:Propylthiouracil