Atorvastatin attenuates hypoxic pulmonary hypertension in rats by inhibiting RhoA/Rho kinase pathway.
10.3969/j.issn.1672-7347.2011.01.009
- Author:
Li DAI
1
;
Shangjie WU
Author Information
1. Department of Respiratory, Second Xiangya Hospital, Central South University, Changsha 410011, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Anticholesteremic Agents;
pharmacology;
Atorvastatin;
Hemodynamics;
Heptanoic Acids;
pharmacology;
Hypertension, Pulmonary;
enzymology;
etiology;
physiopathology;
Hypoxia;
complications;
Male;
Pulmonary Artery;
enzymology;
Pyrroles;
pharmacology;
Random Allocation;
Rats;
Rats, Wistar;
Signal Transduction;
drug effects;
Ventricular Remodeling;
drug effects;
rho-Associated Kinases;
metabolism;
rhoA GTP-Binding Protein;
metabolism
- From:
Journal of Central South University(Medical Sciences)
2011;36(1):58-63
- CountryChina
- Language:Chinese
-
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.
CONCLUSION: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.
