Abstract
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).
Methods and 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.
MeSH terms
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Animals
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Antihypertensive Agents / pharmacology*
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Arterioles / drug effects
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Arterioles / pathology
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Caspase 3 / genetics
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Connexin 43 / metabolism
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Disease Models, Animal
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Heart Ventricles / drug effects*
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Heart Ventricles / metabolism
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Heart Ventricles / physiopathology
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Hypertension, Pulmonary / chemically induced
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Hypertension, Pulmonary / drug therapy*
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Hypertension, Pulmonary / metabolism
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Hypertension, Pulmonary / physiopathology
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Hypertrophy, Right Ventricular / chemically induced
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Hypertrophy, Right Ventricular / metabolism
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Hypertrophy, Right Ventricular / physiopathology
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Hypertrophy, Right Ventricular / prevention & control*
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Lung / blood supply
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Lung / drug effects*
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Lung / metabolism
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Male
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Matrix Metalloproteinase 9 / genetics
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Monocrotaline
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Nitric Oxide Synthase Type III / genetics
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Propylthiouracil / pharmacology*
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Protein Kinase C-epsilon / metabolism
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Proto-Oncogene Proteins c-bcl-2 / genetics
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RNA, Messenger / metabolism
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Rats
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Rats, Sprague-Dawley
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Time Factors
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Tumor Necrosis Factor-alpha / genetics
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Ventricular Function, Right / drug effects
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Ventricular Pressure / drug effects
Substances
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Antihypertensive Agents
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Connexin 43
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Proto-Oncogene Proteins c-bcl-2
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RNA, Messenger
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Tumor Necrosis Factor-alpha
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Propylthiouracil
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Monocrotaline
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Nitric Oxide Synthase Type III
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Nos3 protein, rat
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Prkce protein, rat
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Protein Kinase C-epsilon
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Casp3 protein, rat
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Caspase 3
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Matrix Metalloproteinase 9