Atorvastatin attenuates hypoxic pulmonary hypertension in rats by inhibiting RhoA/Rho kinase pathway

Abstract

To investigate whether atorvastatin treatment can improve the symptoms of hypoxia-induced pulmonary hypertension in rats by inhibiting RhoA/Rho kinase pathway. 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. 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. 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.