钙激活氯离子通道对大鼠肺动脉张力的调节作用

ROLE OF CALCIUM-ACTIVATED CHLORIDE CHANNELS IN THE REGULATION OF PULMONARY VASCULAR TONE IN RATS

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)i、ndaryloxyacetic 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([Ca2+]i)的影响,用荧光分光光度计法检测[Ca2+]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[Ca2+]i升高,NFA和IAA-94对PE诱导[Ca2+]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。

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.