99 TANSHINONE IIA ATTENUATED HYPOXIA-INDUCED PULMONARY HYPERTENSION VIA UPGRADING KV CHANNELS AND P27KIP1

Abstract

Objectives: Pulmonary hypertension induced by hypoxia is the characterized by hypoxic pulmonary vasoconstriction (HPV) and pulmonary vascular structure remodeling (PVSR). Tanshinone IIA (TIIA) has numerous biological protective effects. Purpose of the paper is to investigated whether KV channels and P27kip1 were responsible for the protective effect of TIIA on HPV and PVSR. Basic procedures and methods: Effects of TIIA on intrapulmonary arteriole (IPA) rings and the IKV currents of pulmonary artery smooth muscle cells (PASMCs) isolated from rats in acute hypoxia experiments and chronic hypoxia experiments were determined. Main findings: results showed that TIIA attenuated acute hypoxia-induced IPA rings vasoconstriction which may be partially through recovering the down- regulation of IKV currents in PASMCs. TIIA markedly alleviated the increased weight of right ventricle/left ventricle plus septum ratio, medial width of pulmonary arterioles, decreased expression of Kv2.1 and Kv1.5 and the down-regulation of IKV currents induced by chronic hypoxia. In addition, TIIA increased the p27kip1 protein amount, but did not affect the p27kip1 mRNA amount. TIIA kept p27kip1 from being degraded through repressing the activity of Akt and decreasing the production of Skp-2. Conclusions: Principle conclusions: these data demonstrates that TIIA significantly attenuated acute and chronic hypoxia-induced HPV and PVSR, which were probably through up-regulation KV channels and p27kip1.