The Role Of Kv1.5 And Kv2.1 In The Development Of High Altitude Hypoxic Pulmonary Artery Hypertension And Regression

ObjectiveTo investigate the effect of Kv1.5 and Kv2.1 channel gene expression in the development of pulmonary arterial hypertension (PAH) and regression in hypobaria and hypoxia rats. The relation of Kv1.5 and Kv2.1 gene expression and pulmonary artery(PA) remodeling, the dichloroacetate(DCA) on the Kv1.5 and Kv2.1 expression in pulmonary arterial smooth muscle cells(PASMCs) and mean pulmonary arterial pressure(mPAP), and effect on the PA's remodeling.Methods32 adult male Sprague-Dawley rats (200-250g) were randomly and averagely divided into four groups (n=8 per group):normal group (N group), chronic hypoxia group (CH group), DCA treated group (CH+DCA group), and chronic hypoxia return to normal conditions 7 d group (CHR7). In the CH, CH+DCA and CHR7 groups, 5,000 meter high altitude circumstance was simulated by exposure rats in a hypobaric and hypoxia chamber for 21 days. Rats in N group were fed in normal air pressure and PO2 conditions. N, CH and CH+DCA groups were sacrificed for mPAP measurement and tissue harvest at day 21, The mPAP measurement and tissue harvest of CHR7 group were performed after the rats returned to normal conditions for 7 days. percentage of wall thickness (WT%) and percentage of wall area (WA%) pulmonary arteriole, mPAP, and the ratio of right ventricle/left ventricle and septum, (RV/LV+S) were evaluated, Real- time PCR, immunohistochemistry and western blot were carried out to detect the Kv1.5 and Kv2.1 expression in PASMCs. ResultsIn the CH group, WT%, and WA% of the pulmonary arteriole, mPAP and RV/(LV+S) all increased significantly compared with the N group(P<0.01). These changes in the DCA group were significantly compared with the N group(P<0.01), and PAs and RV remodeling begen to restore in the CHR7 group, mRNA and protein of the Kv1.5 and Kv2.1 in the PASMCs in CH rats were deceased significantly,. However, compared with the CH rats, Kv2.1 mRNA and protein of the CH+DCA group and CHR7 group were restored and mPAP were decreased, and the pulmonary artery wall thicken was slightly.Conclusions1. In the hypobaria and hypoxia circumstance of the a high altitude, the mPAP increase of rats, we scuccuding in estate the PAH animal modeling.2. The gene expression of the Kv1.5 and Kv2.1 of the hypoxia rats, and the PAs wall thickened,remodeling of the PAs, but the Kv1.5 and Kv2.1 gene upreglate followed the mPAP decrease and PAs remodeling decrease, the expression of Kv1.5 and Kv2.1 is negatively correlated with the chronic hypoxia hypertension.3. It maybe a new ideal for the Kv1.5 and Kv2.1 gene expression. DCA inhibit the remodeling of pulmonary arterials probably by recovering Kv1.5 and Kv2.1 expression.