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首页> 外文期刊>Pulmonary pharmacology & therapeutics >Docosahexaenoic acid attenuates hypoxic pulmonary vasoconstriction by activating the large conductance Ca2+-activated K+ currents in pulmonary artery smooth muscle cells
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Docosahexaenoic acid attenuates hypoxic pulmonary vasoconstriction by activating the large conductance Ca2+-activated K+ currents in pulmonary artery smooth muscle cells

机译：二十二碳六烯酸通过激活肺动脉平滑肌细胞中的大电导Ca2 +激活的K +电流来减轻缺氧性肺血管收缩

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Background: The inhibition of potassium (K+) channels plays an important role in pulmonary circulation for its close relationship with hypoxic pulmonary vasoconstriction (HPV). Docosahexaenoic acid (DHA), a n-3 polyunsaturated fatty acid, is well known for its prevention and treatment of cardiovascular diseases. However the role which DHA plays in HPV remains unclear. Here, we tested the hypothesis that DHA contributes to pulmonary vascular tone by activating the large conductance Ca2+-activated K+ (BKCa) channels via calcium sparks. Methods and results: Isolated resistance pulmonary artery preparation was used to study the vasomotor response to DHA. Pulmonary artery smooth muscle cells (PASMCs) were isolated from third- to fourth order branches of pulmonary arteries by collagenase digestion method. BKCa and the voltage-dependent potassium channel (Kv) currents in PASMCs were measured by the whole-cell patch-clamp technique. Fluo-8 was used as a fluorescence indicator for the real-time measurement of calcium dynamics in PASMCs. DHA dilated resistance pulmonary arteries in a dose-dependent manner in hypoxic or normoxic solution, and the effects of DHA were abolished after pre-treatment with heparin (100 μg/ml), a 1,4,5-triphosphate (IP3) receptor (IP3R) inhibitor or iberiotoxin (100 nmol/L), a specific inhibitor of BKCa channel. DHA activated BKCa channels in a dose-dependent manner, however, the activation induced by DHA was not seen in PASMCs pre-incubated with heparin. While the Kv currents decreased from 102.6 ± 5.4 to 36.5 ± 6.7 pA/pF by addition of 10 μmol/L DHA. DHA also caused calcium sparks in PASMCs. Moreover, hypoxia inhibited BKCa currents in PASMCs, but this inhibition was reversed by DHA. Conclusion: Our findings suggest that DHA is a novel BKCa opener in PASMCs, which may indicate a potential therapeutic role in HPV.
机译：背景：钾（K +）通道的抑制作用在肺循环中起着重要作用，因为它与低氧性肺血管收缩（HPV）密切相关。二十二碳六烯酸（DHA）是一种n-3多不饱和脂肪酸，以预防和治疗心血管疾病而闻名。但是，DHA在HPV中的作用尚不清楚。在这里，我们测试了DHA通过钙火花激活大电导Ca2 +激活的K +（BKCa）通道而有助于肺血管紧张的假设。方法与结果：采用隔离阻力肺动脉制剂研究对DHA的血管舒缩反应。通过胶原酶消化法从肺动脉三至四级分支中分离出肺动脉平滑肌细胞（PASMC）。通过全细胞膜片钳技术测量PASMC中的BKCa和电压依赖性钾通道（Kv）电流。 Fluo-8用作荧光指示剂，用于实时测量PASMC中钙动力学。 DHA在低氧或高氧溶液中以剂量依赖的方式扩张了肺动脉的抵抗力，在用1,400,5-三磷酸（IP3）受体肝素（100μg/ ml）预处理后，DHA的作用消失了（ IP3R）抑制剂或iberiotoxin（100 nmol / L），BKCa通道的特异性抑制剂。 DHA以剂量依赖性方式激活BKCa通道，但是，在与肝素预孵育的PASMC中未观察到DHA诱导的激活。通过添加10μmol/ L DHA，Kv电流从102.6±5.4降至36.5±6.7 pA / pF。 DHA还会在PASMC中引起钙火花。此外，低氧抑制了PASMCs中BKCa电流，但DHA逆转了这种抑制作用。结论：我们的发现表明DHA是PASMC中的新型BKCa开启剂，可能表明其对HPV有潜在的治疗作用。

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