Propylthiouracil attenuates monocrotaline-induced pulmonary arterial hypertension in rats.
BACKGROUND
Propylthiouracil (PTU) enhances nitric oxide production and inhibits smooth muscle cell proliferation, suggesting a possible role in the prevention of pulmonary arterial hypertension (PAH).


RESULTS
The 30 male Sprague-Dawley rats were randomized to receive saline injection only (group 1), monocrotaline (MCT) (70 mg/kg) only (group 2) or MCT + 0.1% PTU in drinking water (group 3) given on day 5 after MCT administration. By day 35, western blot showed lower connexin43 (Cx43) and membranous protein kinase C-epsilon expressions in the right ventricle (RV) of group 2 animals than in the other groups (all P<0.05). Conversely, Cx43 expression in the lung was higher in group 2 than in other groups (all P<0.02). Additionally, mRNA expressions of matrix metalloproteinase-9, tissue necrotic factor-alpha, and caspase-3 were higher, whereas Bcl-2 and endothelial nitric oxide synthase were lower, in the lungs and RV of group 2 rats than in the other groups (all P<0.05). Moreover, the numbers of alveolar sacs and lung arterioles were also reduced in group 2 than in other groups (all P<0.05), and RV systolic pressure and RV weight were increased in group 2 compared with other groups (all P<0.001).


CONCLUSIONS
PTU effectively attenuates complications associated with MCT-induced PAH.
Sun
Cheuk-Kwan
CK
Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Yuen
Chun-Man
CM
Kao
Ying-Hsien
YH
Chang
Li-Teh
LT
Chua
Sarah
S
Sheu
Jiunn-Jye
JJ
Yen
Chia-Hung
CH
Ko
Sheung-Fat
SF
Yip
Hon-Kan
HK
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001160:Arterioles / Q000187:drug effects / Q000473:pathology; D053148:Caspase 3 / Q000235:genetics; D018031:Connexin 43 / Q000378:metabolism; D004195:Disease Models, Animal; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D016686:Monocrotaline; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D011441:Propylthiouracil / Q000494:pharmacology*; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D016278:Ventricular Function, Right / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
D000959:Antihypertensive Agents; D018031:Connexin 43; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D011441:Propylthiouracil; D016686:Monocrotaline; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C497257:Prkce protein, rat; D051744:Protein Kinase C-epsilon; C505410:Casp3 protein, rat; D053148:Caspase 3; D020780:Matrix Metalloproteinase 9