title: [Atorvastatin attenuates hypoxic pulmonary hypertension in rats by inhibiting RhoA/Rho kinase pathway].
abstract: OBJECTIVE
  To investigate whether atorvastatin treatment can improve the symptoms of hypoxia-induced pulmonary hypertension in rats by inhibiting RhoA/Rho kinase pathway.
  
  
  METHODS
  A total of 32 Westar rats was divided into 4 groups: normoxic controls (Group A), hypoxic controls (Group B), hypoxia plus atorvastatin [10 mg/(kg.d)] group(Group C), and hypoxia plus the vehicle of atorvastatin (Group D). Rats for hypoxia treatment were maintained under the condition of 10% FiO2 6 h/d for 4 weeks. At the end of 4 weeks, rats were anesthetized and the mean pulmonary arterial pressure (mPAP) was measured by right heart catheterization. The ratios of arteriole wall thickness to vascular external diameter (WT%), and vascular area to total vascular area (WA%) were measured by a computerized image analyzer. RhoA and phos-MYPT-1 expression in the pulmonary artery were determined by Western blot.
  
  
  RESULTS
  Comparing with Group A, the mPAP [(29.6 ± 1.1)mmHg vs (16.8 ± 0.7)mmHg], RV/(LV+S) [(39.0 ± 0.7)%vs (29.4 ± 0.5)%], WT% [(35.6 ± 2.4)% vs (22.3 ± 1.2)%] and WA% [(56.5 ± 5.1)% vs (36.6 ± 2.3)%] in Group B were all significantly increased (P<0.05). Comparing with Group B, the mPAP [(25.3 ± 3.2)mmHg], RV/(LV+S) [(36.3 ± 2.1)%], WT%[(29.2 ± 3.2)%] and WA% [(48.1 ± 2.7)%] in Group C were significantly decreased. The vehicle of atorvastatin had no such effect. The expression of RhoA and phos-MYPT-1 in the pulmonary artery was increased in Group B, but it was decreased in Group C.
  
  
  CONCLUSIONS
  RhoA/Rho kinase pathway plays an important role in the development of hypoxic pulmonary hypertension. Atorvastatin can improve the symptoms of hypoxic pulmonary hypertension by inhibiting RhoA/Rho kinase activity.
authors.affiliation: Department of Respiratory, Second Xiangya Hospital, Central South University, Changsha 410011, China.
authors.forename: Li
authors.initials: L
authors.lastname: Dai
authors.forename: Shangjie
authors.initials: S
authors.lastname: Wu
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D000069059:Atorvastatin; D006439:Hemodynamics; D006538:Heptanoic Acids / Q000494:pharmacology*; D006976:Hypertension, Pulmonary / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications*; D008297:Male; D011651:Pulmonary Artery / Q000201:enzymology; D011758:Pyrroles / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein