title: The effects of the 5-HT2A receptor antagonist sarpogrelate hydrochloride on chronic hypoxic pulmonary hypertension in rats.
abstract: This study investigated whether sarpogrelate hydrochloride (SPG), a 5-HT2A receptor antagonist, alleviates chronic hypoxic pulmonary hypertension (CH-PH) in rats by stimulating apoptosis and inhibiting proliferation in pulmonary artery smooth muscle cells (PASMCs).
  
  
  
  Forty male Sprague-Dawley rats were pretreated with SPG (50 mg/kg/day by oral gavage) or saline vehicle and then subjected to chronic hypoxia (CH) (hypobaric chamber set to 380 mmHg, 10% oxygen) or normoxia for 14 days. Mean pulmonary artery pressure (PAP) and right ventricular hypertrophy (RVH) were measured. Hypertensive pulmonary vascular remodeling was assayed by light microscopy. Terminal deoxynucletidyl transferase dUTP nick end ligase (TUNEL) assays, western blotting, and real-time polymerase chain reaction were used to assess apoptosis, proliferation and underlying signaling pathways in PASMCs from lung tissue and isolated pulmonary artery rings.
  
  
  
  CH increased mean PAP and RVH. CH increased the percentage of muscularized arteries in the peripheral pulmonary vasculature and medial wall thickness in small muscular arteries. CH increased pulmonary protein and mRNA levels of the B-cell lymphoma protein 2 (Bcl-2), pyruvate dehydrogenase kinase (PDK), phosphorylation of extracellular signal-regulated kinases 1 and 2 (pERK1/2), cyclin D1, proliferating cell nuclear antigen (PCNA) and decreased protein and mRNA levels of Bcl-2-associated X protein (BAX), cleaved caspase-3. Pretreatment with SPG, which has been shown previously to inhibit ERK1/2 phosphorylation and PDK, countered all of these effects. Isolated pulmonary artery rings incubated with 5-HT increased pERK1/2, PDK, and Bcl-2 expression, and decreased Bax expression.
  
  
  
  Administration of SPG ameliorated the development of CH-PH by stimulating apoptosis in and inhibiting proliferation of PASMCs.
authors.affiliation: a Department of Peripheral Vascular Disease , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi , China.
authors.forename: Jie
authors.initials: J
authors.lastname: Geng
authors.affiliation: a Department of Peripheral Vascular Disease , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi , China.
authors.forename: Fen-Ling
authors.initials: FL
authors.lastname: Fan
authors.affiliation: b Department of Breast Cancer , Shaanxi Provincial Tumor Hospital , Xi'an, Shaanxi , China.
authors.forename: Sai
authors.initials: S
authors.lastname: He
authors.affiliation: a Department of Peripheral Vascular Disease , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi , China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Liu
authors.affiliation: a Department of Peripheral Vascular Disease , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Meng
authors.affiliation: a Department of Peripheral Vascular Disease , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi , China.
authors.forename: Hua
authors.initials: H
authors.lastname: Tian
authors.affiliation: a Department of Peripheral Vascular Disease , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi , China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: a Department of Peripheral Vascular Disease , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi , China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ma
authors.affiliation: a Department of Peripheral Vascular Disease , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi , China.
authors.forename: Jun-Bo
authors.initials: JB
authors.lastname: Zhang
authors.affiliation: a Department of Peripheral Vascular Disease , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi , China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Tian
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002908:Chronic Disease; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D000860:Hypoxia; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D011292:Premedication; D011651:Pulmonary Artery / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology*; D013386:Succinates / Q000494:pharmacology*
chemical_list: D058830:Serotonin 5-HT2 Receptor Antagonists; D013386:Succinates; C064294:sarpogrelate
keywords: apoptosis; hypoxia; pulmonary hypertension; sarpogrelate hydrochloride; serotonin 2A receptor