title: Effects and mechanism of oridonin on pulmonary hypertension induced by chronic hypoxia-hypercapnia in rats.
abstract: BACKGROUND
  Pulmonary arterial hypertension (PAH) is characterized by suppressing apoptosis and enhancing cell proliferation in the vascular wall. Inducing pulmonary artery smooth muscle cells (PASMC) apoptosis had been regarded as a therapeutic approach for PAH. Oridonin can cause apoptosis in many cell lines, while little has been done to evaluate its effect on PASMC.
  
  
  METHODS
  Thirty male Sprague-Dawley rats were randomly assigned to three groups: normal control (NC); hypoxia-hypercapnia (HH); Hypoxia-hypercapnia + oridonin (HHO). Rats were exposed to hypoxia-hypercapnia for four weeks. Cultured human PASMC (HPASMC) were assigned to three groups: normoxia (NO); hypoxia (HY); hypoxia + oridonin (HO). The mean pulmonary artery pressure, mass ratio of right ventricle over left ventricle plus septum (RV/(LV + S)), the ratio of thickness of the pulmonary arteriole wall to vascular external diameter (WT%) and the ratio of the vessel wall area to the total area (WA%) were measured. Morphologic changes of pulmonary arteries were observed under light and electron microscopes. The apoptotic characteristics in vitro and in vivo were detected.
  
  
  RESULTS
  The mPAP, RV/(LV + S), WT%, and WA% in the HH group were significantly greater than those in the NC (P < 0.01) and HHO groups (P < 0.01); the activities of caspase-3 and caspase-9, and the expressions of Bax, cyt-C and apoptotic index (AI) in the group HH were less than those in the NC and HHO groups; and the expression of Bcl-2 in group HH was greater than that in the NC and HHO groups. HPASMC mitochondrial membrane potentials in group HO was lower than in group HY (P < 0.01), and cyt-C in the cytoplasm, AI, and caspase-9 in the HO group were greater than that in the HY group (P < 0.01), but the expression of Bcl-2 in the HO group was less than that in the HY group (P < 0.05).
  
  
  CONCLUSIONS
  The results suggest that oridonin can lower pulmonary artery pressure effectively, and inhibit pulmonary artery structural remodeling by inducing smooth cell apoptosis via a mitochondria-dependent pathway.
authors: Department of Respiratory Medicine, First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325003, China. 38805@163.com
authors: Liang-Xing
authors: LX
authors: Wang
authors: Yu
authors: Y
authors: Sun
authors: Chan
authors: C
authors: Chen
authors: Xiao-Ying
authors: XY
authors: Huang
authors: Quan
authors: Q
authors: Lin
authors: Guo-Qing
authors: GQ
authors: Qian
authors: Wei
authors: W
authors: Dong
authors: Yan-Fan
authors: YF
authors: Chen
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D017209:Apoptosis; D015153:Blotting, Western; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D006935:Hypercapnia / Q000503:physiopathology*; D006976:Hypertension, Pulmonary / Q000188:drug therapy; D000860:Hypoxia / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D053078:Membrane Potential, Mitochondrial; D008853:Microscopy; D046529:Microscopy, Electron, Transmission; D011651:Pulmonary Artery / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000959:Antihypertensive Agents; D045786:Diterpenes, Kaurane; C011959:oridonin