title: Aspirin attenuates monocrotaline-induced pulmonary arterial hypertension in rats by suppressing the ERK/MAPK pathway.
abstract: This study aimed to investigate the therapeutic effects of aspirin (ASA) and its potential mechanisms of action in monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats. PAH was induced in a rat model by a single intraperitoneal (IP) injection of MCT. Saline was injected in a control group. Two weeks following MCT injection, right ventricular systolic pressure (RVSP) and systolic blood pressure (SBP) were measured in six rats from each group to confirm establishment of a PAH model. The remaining MCT-treated rats were randomly allocated to receive IP injection of saline, ASA, or ERK1/2 inhibitor PD98059. Four weeks following treatment, RVSP was measured and all rats were sacrificed for histological study. There was no significant difference in SBP in any group two weeks following MCT administration. Nonetheless RVSP was significantly increased in the MCT group compared with the control group. At 6 weeks, ASA treatment remarkably attenuated MCT-induced increased RVSP, RV hypertrophy, and pulmonary artery remodeling compared with the MCT group. The density of pulmonary capillaries in ASA-treated rats was also dramatically increased. Treatment with ASA significantly inhibited the increased p-ERK1/2 and restored the impaired endothelial nitric oxide synthase (eNOS) in MCT-treated rats. This study demonstrated that ASA distinctively attenuates MCT-induced PAH by inhibition of the ERK1/2 signaling pathway.
authors.affiliation: a Department of Respiration , First Affiliated Hospital of Bengbu Medical College, Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease , Bengbu , Anhui , P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Gao
authors.affiliation: a Department of Respiration , First Affiliated Hospital of Bengbu Medical College, Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease , Bengbu , Anhui , P.R. China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: b Department of Intensive Care Unit , Zaozhuang Municipal Hospital , Zaozhuang , Shandong , P.R. China.
authors.forename: Liguo
authors.initials: L
authors.lastname: Zong
authors.affiliation: a Department of Respiration , First Affiliated Hospital of Bengbu Medical College, Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease , Bengbu , Anhui , P.R. China.
authors.forename: Linian
authors.initials: L
authors.lastname: Huang
authors.affiliation: c Department of Cardiology , First Municipal Hospital of Bengbu , Bengbu , Anhui , P.R. China.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Qiao
authors.affiliation: a Department of Respiration , First Affiliated Hospital of Bengbu Medical College, Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease , Bengbu , Anhui , P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: a Department of Respiration , First Affiliated Hospital of Bengbu Medical College, Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease , Bengbu , Anhui , P.R. China.
authors.forename: Beilei
authors.initials: B
authors.lastname: Gong
authors.affiliation: a Department of Respiration , First Affiliated Hospital of Bengbu Medical College, Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease , Bengbu , Anhui , P.R. China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Hu
authors.affiliation: a Department of Respiration , First Affiliated Hospital of Bengbu Medical College, Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease , Bengbu , Anhui , P.R. China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Liu
authors.affiliation: a Department of Respiration , First Affiliated Hospital of Bengbu Medical College, Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease , Bengbu , Anhui , P.R. China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Wang
authors.affiliation: a Department of Respiration , First Affiliated Hospital of Bengbu Medical College, Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease , Bengbu , Anhui , P.R. China.
authors.forename: Chengling
authors.initials: C
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D005419:Flavonoids / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy*; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000188:drug therapy*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D016686:Monocrotaline; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013599:Systole; D066253:Vascular Remodeling / Q000187:drug effects
chemical_list: D016861:Cyclooxygenase Inhibitors; D005419:Flavonoids; D047428:Protein Kinase Inhibitors; D016686:Monocrotaline; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D001241:Aspirin; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: Aspirin; ERK1/2; nonsteroidal anti-inflammatory drugs; pulmonary arterial hypertension