title: [Protective effects of beraprost plus simvastatin on monocrotaline-induced pulmonary arterial hypertension in rats].
abstract: OBJECTIVE
  To explore the protective effects of beraprost plus simvastatin on monocrotaline-induced pulmonary arterial hypertension in rats.
  
  
  METHODS
  Forty male Sprague-Dawley rats were allocated to control (C), untreated pulmonary arterial hypertension (P), beraprost (B), simvastatin (S) and combination groups (Com) (n = 8 each). Normal saline was injected subcutaneously into group C and then there was no other intervention for 21 days. Group P, B, S and Com rats received subcutaneous injections of monocrotaline (MCT, 60 mg/kg) and then isovolumetric normal saline, beraprost (100 µg·kg(-1)·d(-1)), simvastatin (2 mg·kg(-1)·d(-1)) and beraprost (100 µg·kg(-1)·d(-1)) plus simvastatin (2 mg·kg(-1)·d(-1)) by daily gastric lavage for 21 days. At Day 22, heart rate (HR), mean arterial pressure (MAP) and mean pulmonary pressure (mPAP) were detected and right heart ventricular hypertrophy index (RVHI) was calculated. The histopathology changes and tunica media thickness percentage of pulmonary arteries (WT%) were evaluated by pulmonary tissue staining. The results were analyzed statistically.
  
  
  RESULTS
  The differences of HR and MAP were not significant among 5 groups (all P > 0.05). The levels of mPAP, RVHI and WT% in group B ((27.4 ± 3.7) mm Hg, 0.35 ± 0.03, 26.7% ± 2.4%), group S ((29.9 ± 4.4) mm Hg, 0.36 ± 0.03, 28.2% ± 1.9%) and group Com ((23.1 ± 3.9) mm Hg, 0.32 ± 0.03, 17.4% ± 3.3%) were lower than those in group P ((35.4 ± 5.7) mm Hg, 0.41 ± 0.05, 42.8% ± 5.9%) (all P < 0.05).
  
  
  CONCLUSIONS
  The combined use of beraprost and simvastatin may delay the increase of mPAP and remodeling of pulmonary vessels and inhibit right ventricular hypertrophy in pulmonary arterial hypertension rats. Its efficacy is superior to that of monotherapy.
authors.affiliation: Department of Infection Diseases, Affiliated Beijing Anzhen Hospital, Capital Medical University & Beijing Institute of Heart, Lung & Blood Vessel Diseases, Beijing 100029, China.
authors.forename: Sheng-hao
authors.initials: SH
authors.lastname: Wang
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.forename: Jing-hua
authors.initials: JH
authors.lastname: Yang
authors.forename: Zeng-zhi
authors.initials: ZZ
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Wei-wei
authors.initials: WW
authors.lastname: Hou
mesh_terms: D000818:Animals; D004359:Drug Therapy, Combination; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D016686:Monocrotaline / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: C048081:beraprost; D016686:Monocrotaline; D019821:Simvastatin; D011464:Epoprostenol