钙激活氯离子通道对大鼠肺动脉张力的调节作用

目的：研究钙激活氯离子通道及其通道阻断剂尼氟灭酸（niflumic acid,NFA）、indaryloxyacetic acid（IAA-94）在苯福林（phenylephrine,PE）引起的肺动脉收缩中的作用。方法：常规离体血管灌流法检测肺动脉环张力;采用钙荧光探针（Fura-2／AM）负载急性酶分离法（胶原酶Ⅰ型和木瓜蛋白酶）获得的大鼠肺动脉平滑肌细胞（PASMCs）,观察NFA和IAA-94对PE诱导的PASMCs胞浆游离钙离子浓度（Ca^2＋]i）的影响,用荧光分光光度计法检测Ca^2＋]i。结果：钙激活氯离子通道阻断剂NFA和IAA-94可以舒张PE引起的肺动脉环收缩;NFA和IAA-94对KCl引起的血管收缩无影响;PE可以引起Ca^2＋]i升高,NFA和IAA-94对PE诱导Ca^2＋]i升高无影响。结论：钙激活氯离子通道在生理状态下与血管活性药（PE）引起的肺动脉张力变化有关,这为研究其在低氧肺血管收缩中的作用提供了新的线索。

Role of calcium-activated chloride channels in the regulation of pulmonary vascular tone in rats

Aim: To investigate the role of calcium-activated chloride channels and the Cl-channel blockers niflumic acid(NFA) and indaryloxyacetic acid(IAA-94) in the regulation of vascular contraction induced by phenylephrine(PE).Methods: The PE-induced contraction in rat pulmonary artery was observed by using routine blood vascular perfusion in vitro.The fluorescence Ca~(2+) indicator Fura-2/AM was used to observe intracellular free Ca~(2+) concentration(Ca~(2+)]i) of rat pulmonary artery smooth muscle cells(PASMCs) which were obtained by the acute enzyme separation method(collagnase I plus papain) on NFA and IAA-94 effects on PE-induced contraction.Changes of Ca~(2+)]i in PASMCs were measured by spectrofluorometry.Results: The anion channel blockers NFA and IAA-94 produced inhibitory effects on PE-induced contractions in the pulmonary artery.NFA and IAA-94 negligibly affected the KCl-induced pulmonary artery contractions.PE could increase Ca~(2+)]i but NFA and IAA-94 negligibly affected it.Conclusion: Calcium-activated chloride channels contribute to the agonist-induced pulmonary artery contractions under physiological conditions,which may be a new clue to investigate the hypoxic pulmonary vasoconstriction.