title: Aspirin attenuates pulmonary arterial hypertension in rats by reducing plasma 5-hydroxytryptamine levels.
abstract: Pulmonary arterial hypertension (PAH) is characterized by increasing pulmonary pressure, right ventricular failure, and death. The typical pathological changes include medial hypertrophy, intimal fibrosis and in situ thrombosis. Serotonin (5-HT) and other factors contribute to the development of pathologic lesions. Aspirin (ASA), a platelet aggregation inhibitor, inhibits 5-HT release from platelets. The aim of this study was to determine the efficacy of ASA in preventing or attenuating PAH. Sprague-Dawley rats injected with monocrotaline (MCT) developed severe PAH within 31 days. One hundred forty rats were randomized to receive either vehicle or ASA (0.5, 1, 2, or 4 mg/kg/day). The pre-ASA group was treated with ASA (1 mg/kg/day) for 30 days before the MCT injection. Thirty-one days after the injection (day 61 for the pre-ASA group), pulmonary arterial pressure (PAP), right ventricular hypertrophy and pulmonary arteriole thickness were measured. Plasma 5-HT was measured by high-performance liquid chromatography. Aspirin suppressed PAH and increased the survival rate compared with the control group (84 vs. 60%, P < 0.05). Aspirin treatment also reduced right ventricular hypertrophy and pulmonary arteriole proliferation in ASA-treated PAH model. In addition, plasma 5-HT was decreased in our ASA-treated PAH model. The degree of 5-HT reduction was associated with systolic PAP, right ventricular hypertrophy and wall thickness of pulmonary arterioles in rats. These results showed that ASA treatment effectively attenuated MCT-induced pulmonary hypertension, right ventricular hypertrophy, and occlusion of the pulmonary arteries. The effects of ASA was associated with a reduction of 5-HT.
authors.affiliation: Cardiovascular Department, Renji Hospital, Shanghai Jiaotong University School of Medicine, Dong Fang Road 1630, Shanghai 200127, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Shen
authors.forename: Jieyan
authors.initials: J
authors.lastname: Shen
authors.forename: Jun
authors.initials: J
authors.lastname: Pu
authors.forename: Ben
authors.initials: B
authors.lastname: He
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology* / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D016686:Monocrotaline; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011651:Pulmonary Artery / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000097:blood*; D016019:Survival Analysis
chemical_list: D010975:Platelet Aggregation Inhibitors; D012701:Serotonin; D016686:Monocrotaline; D001241:Aspirin