Atorvastatin attenuates involvement of RhoA/Rho-kinase pathway and NF-κB activation in hypoxic pulmonary hypertensive rats / 中华医学杂志(英文版)

ABSTRACT

<p><b>BACKGROUND</b>Hypoxic pulmonary hypertension (HPH) contributes to the pathogenesis of cardiopulmonary diseases. Several lines of evidence indicate that the Rho A/Rho-kinase pathway play an important role in the progress of pulmonary hypertension. Stains have been shown exert numerous biological effects that are independent of their cholesterol-lowering property. We hypothesized that the Rho A/Rho-kinase pathway is involved in the pathogenesis of HPH, and that atorvastatin would attenuate involvement of the Rho A/Rho-kinase pathway in a HPH rat model.</p><p><b>METHODS</b>Thirty-two Wistar rats were randomly divided into four groups control group, hypoxic group, atovastatin group, and normal saline group. The control group was kept in a normoxia environment. The other groups were exposed to hypoxia for three weeks. Atovastatin was administered daily via a gastric gavage in the atovastatin group. We measured the mean pulmonary arterial pressure (mPAP), the ratio of the right ventricular weight to the sum of the weights of the left heart ventricle and septum (RV/(LV+S)), arteriole wall thickness/vascular external diameter (WT%), vascular area/total vascular area (WA%), expression of RhoA and phos-MYPT-1 protein in lung tissue, and NF-κB activation in pulmonary vascular smooth muscle cells.</p><p><b>RESULTS</b>Compared with the control group, mPAP, RV/(LV+S), WT%, WA%, NF-κB activation, expression of RhoA, and phos-MYPT-1 were increased in the hypoxic and normal saline groups (P < 0.05). Compared with the hypoxic group, mPAP, RV/(LV+S), WT%, WA%, NF-κB activation, expression of RhoA, and phos-MYPT-1 were decreased in the atovastatin group (P < 0.05). Correlations between phos-MPTY-1 and mPAP, WA%, WT%, and NF-κB activation were all positive.</p><p><b>CONCLUSIONS</b>The Rho A/Rho-kinase pathway plays an important role in the development of HPH. Atorvastatin reversed HPH by inhibiting the activity of Rho A/Rho-kinase and NF-κB.</p>