propylthiouracil and Hypertrophy--Right-Ventricular

Propylthiouracil (PTU) enhances nitric oxide production and inhibits smooth muscle cell proliferation, suggesting a possible role in the prevention of pulmonary arterial hypertension (PAH).. 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).. PTU effectively attenuates complications associated with MCT-induced PAH.

Topics: Animals; Antihypertensive Agents; Arterioles; Caspase 3; Connexin 43; Disease Models, Animal; Heart Ventricles; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Lung; Male; Matrix Metalloproteinase 9; Monocrotaline; Nitric Oxide Synthase Type III; Propylthiouracil; Protein Kinase C-epsilon; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; RNA, Messenger; Time Factors; Tumor Necrosis Factor-alpha; Ventricular Function, Right; Ventricular Pressure