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Kv3.4 channel is involved in rat pulmonary vasoconstriction induced by 15--hydroxyeicosatetraenoic acid

Li Qian, Bi Hairong, Zhang Rong, Zhu Daling

College of Pharmacy. Harbin China；The Pharmarceutical Department of the Second Affiliated Hospital，Harbin Medical University. Harbin, China；Biopharmacy Engineering Key Laboratory of Heilongjiang Province. Harbin 150086, China

Abstract

We have reported that hypoxia increases the activation of 15-lipoxygenase (15-LO), which converts arachidonic acid (AA) into 15-hydroxyeicosatetraenoic acid (15-HETE) in small pulmonary arteries (PAs). Through inhibition of Kv channels, 15-HETE causes more robust concentration-dependent contraction of PA rings from the hypoxic compared to the normoxic controls. However, the subtypes of Kv channels inhibited by 15-HETE are incompletely understood. The aim of the present study was to identify the contribution of Kv3.4 channel in the process of pulmonary vasoconstriction induced by 15-HETE using the tension studies of PA rings from rat with Kv3.4 channel blocker in tissue bath; to explore the role of vascular endothelium in15-HETE-induced pulmonary vasoconstriction through denuded endothelia of PA rings; and to define the downregulation of 15-HETE on the expression of Kv3.4 channel in cultured pulmonary artery smooth muscle cells (PASMCs) with RT-PCR and Western blot. In the present study, healthy Wistar rats were divided randomly into two groups: Group A with normal oxygen supply and group B with hypoxia. Six days later, the rats were killed. Pulmonary artery rings were prepared for organ bath experiments. Firstly, different concentrations of 15-HETE (10~1 000 nmol/L) were added to the Krebs solution. The isometric tension was recorded using a four-channel force-displacement transducer. Then Kv3.4 channel blocker, 100 nmol/L BDS-Ⅰ, was added, followed by adding 1 mmol/L 15-HETE, and the isometric tension was recorded. Furthermore, RT-PCR and Western blot were employed to identify the influence of 15-HETE on the expression of Kv3.4 channel in cultured rat PASMCs.The results showed the PA tension was significantly increased both in groups A and B by 15-HETE in a concentration-dependent manner (P<0.05), especially in group B (P<0.05 compared to control); denuded endothelia enhanced 15-HETE concentration-related constrictions in rat PA rings; Kv3.4 channel blocker, BDS-Ⅰ, significantly decreased the PA ring constriction induced by 15-HETE (P<0.05); the expressions of Kv3.4 mRNA and protein in rat PASMCs were significantly downregulated by 15-HETE (P<0.05). Based on all the information above, we conclude that Kv3.4 channel is involved in vasoconstriction induced by 15-HETE in rat PAs.

Key words: 15-hydroeicosatetraenoic acid;Vvoltage-gated potassium channel subunits;Pulmonary artery smooth muscle cells;Hypoxic pulmonary vasoconstriction

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Citing This Article：

Li Qian, Bi Hairong, Zhang Rong, Zhu Daling. Kv3.4 channel is involved in rat pulmonary vasoconstriction induced by 15--hydroxyeicosatetraenoic acid. Acta Physiol Sin 2006; 58 (1): (in Chinese with English abstract).