尼氟灭酸对急性低氧人肺动脉收缩的影响

摘要

Aim To investigate the effects of nifiumic acid ( NFA ) , an inhibitor of calcium-activated chloride ( ClCa )channels, on pulmonary vasoconstriction of human in acute hypoxic conditions. Methods Acute hypoxia-induced contraction was observed in human pulmonary artery by using routine blood vascular perfusion in vitro; the fluorescence Ca2+ indicator Fura-2/AM was used to observe intracellular free Ca2+ concentration( [ Caz+ ]i ) in human pulmonary artery smooth muscle cells( PASMCs )through putting into ClCa channel blockers NFA and indaryloxyacetic acid( IAA-94 ) in normal( 37℃ ,5o％ CO2 ,21％ O2 ,74％ N2 )and acute hypoxic( 37℃ ,5％ CO2 ,2％ O2 ,93％ N2 )conditions. Results ① In acute hypoxic condition,[ Ca2+ ]i was increased: in normoxic condition,[ Ca2+ ]i was( 103. 26 ±4. 72 )nmol · L-1 , and in hypoxic condition,[ Caz+ ]i was( 253. 89 ± 9. 82 )nmol ·L-1( P ＜ 0. 01 ); The NFA and IAA-94 decreased [ Ca2+ ]i from( 253. 89 ±9. 82 )nmol . L-1 to( 107. 18 ± 14. 99 )nmol · L-1( P ＜ 0. 01 ). ②Acute hypoxia evoked pulmonary artery contractions from ( 4. 54 ± 0. 52 )g · g-1 to( 49. 51 ± 1. 30 )g · g-1( P ＜ 0. 01 );The NFA and IAA-94 inhibited hypoxia-evoked contractions in the pulmonary artery from( 49. 51 ± 1. 30 )g · g-1 to( 4. 50 ± 0. 40 )g · g-1( P ＜ 0. 01 ). Conclusions NFA can inhibit the contraction of human pulmonary artery in acute hypoxic condition, which may result from the inhibition of activity ClCa channels.%目的 研究钙激活氯离子(ClCa)通道阻滞剂尼氟灭酸(NFA)对急性低氧人肺动脉收缩的影响.方法 在常氧(37℃、5% CO2、21% O2、74% N2)和急性低氧 (37℃、5% CO2、2% O2、93% N2)条件下,采用荧光分光光度计法、离体血管灌流法,观察ClCa阻滞剂NFA和indaryloxyacetic acid(IAA-94)对急性低氧人肺动脉平滑肌细胞质内游离钙离子浓度([Ca2+]i)及肺动脉张力的影响.结果 ① 急性低氧引起[Ca2+]i升高,由常氧时的(103.26±4.72)nmol·L-1升高至(253.89±9.82)nmol·L-1(P<0.01);加入NFA、IAA-94使[Ca2+]i明显下降,最低至(107.18±14.99)nmol·L-1(P<0.01);② 急性低氧引起肺动脉环收缩,由常氧时的(4.54±0.52)g·g-1至最大收缩张力(49.51±1.30)g·g-1(P<0.01);加入NFA和IAA-94后,它们均能抑制由低氧引起的血管收缩,使收缩张力最低降至(4.50±0.40)g·g-1(P<0.01).结论 NFA能有效抑制急性低氧引起的肺动脉收缩,这一效果可能是通过抑制ClCa通道活性来实现的.