Protease inhibitors potentiate smooth muscle relaxation induced by vasoactive intestinal peptide in isolated human bronchi.
Protease inhibitors potentiate smooth muscle relaxation induced by vasoactive intestinal peptide in isolated human bronchi.
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蛋白酶抑制剂增强离体人支气管中血管活性肠肽诱导的平滑肌松弛。
DOI：
10.1165/ajrcmb/2.5.449
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发表时间：
1990
影响因子：
6.4
通讯作者：
Caughey,GH
中科院分区：
文献类型：
--
作者：
Tam,EK;Franconi,GM;Nadel,JA;Caughey,GH
材料和方法取材于5例11 ~ 35岁非吸烟的因原发性或继发性先天性心脏病肺动脉高压而行心肺移植的患者肺组织。没有受试者有气道疾病、感染或左侧充血性心力衰竭的临床证据。移植前的慢性药物包括氧气、速尿、硝化甘油或钾，但不使用皮质类固醇。取肺内大叶和节段性支气管各20个环，连接在应变计上记录等距张力，置于充满Krebs-Henseleit溶液的室中，温度37℃，含5% CO2的O2。将环拉伸至5 g张力，静息张力为1 g平衡15 min，然后用乙酰胆碱（10-3 M）收缩以确定最大收缩量。反复洗涤组织，直到静息张力达到1g。然后与吲哚美辛（2 × 10-6 M; 30 min）、心得安（10-6 M; 15 min）和吡啶胺（10-5 M; 15 min）共同培养，阻断前列腺素、肾上腺素能和组胺I型的作用。加入10-6 ~ 10-5 M的氨甲酰胆碱引起半最大收缩。当活性张力稳定至少5min时，将蛋白酶抑制剂磷酸酰胺、胰肽、抑肽蛋白和大豆胰蛋白酶抑制剂（各20 Itg/ml）添加到9个器官液中。10分钟后，将VIP （5 × 10-7 M）加入所有器官浴中，记录张力变化至少30分钟。张力以加入VIP前立即测量的氨甲酰胆碱诱导（活性）张力的百分比表示。没有用抑制剂治疗的组织，尽管VIP仍然保持或恢复了近100%的主动张力，然后用蛋白酶抑制剂治疗。这些组织包括两个连续的支气管节段，其中上皮已被移除。对VIP和蛋白酶抑制剂的反应记录为at
Materials and Methods Lung tissue was obtained from five nonsmoking patients 11 to 35 yr old undergoing heart-lung transplantation for pulmonary hypertension, either primary or secondary to congenital heart disease. No subject had clinical evidence of airway disease, infection, or left-sided congestive heart failure. Chronic medications before transplantation included oxygen, furosemide, nitroglycerin, or potassium, but no corticosteroids. Twenty rings from intrapulmonary lobar and segmental bronchi were attached to strain gauges to record isometric tension and placed in chambers filled with Krebs-Henseleit solution at 37 C aerated with 5% CO2 in O2• Rings were stretched to a tension of 5 g, equilibrated for 15 min with a resting tension of 1 g, then contracted with acetylcholine (10-3 M) to determine the maximal contraction. The tissues were washed repeatedly until a resting tension of 1 g was achieved. They were then incubated with indomethacin (2 x 10-6 M; 30 min), propranolol (10-6 M; 15 min) and pyrilamine (10-5 M; 15 min) to block prostaglandin, adrenergic, and histamine type I effects. Carbamylcholine (10-6 to 10-5 M) was added to cause half-maximal contraction. When the active tension was stable for at least 5 min, the protease inhibitors phosphoramidon, leupeptin, aprotinin, and soybean trypsin inhibitor (each 20 Itg/ml) were added to nine of the organ baths. Ten minutes later, VIP (5 x 10-7 M) was added to all organ baths, and the change in tension was recorded for at least 30 min. Tension was expressed as the percentage of the carbamylcholine-induced (active) tension measured immediately before the addition of VIP. Tissues that had not been treated with inhibitors and that had maintained or regained nearly 100% of active tension despite VIP were then treated with the protease inhibitors. These tissues included two consecutive segments of bronchus from which the epithelium had been removed. Responses to VIP and protease inhibitors were recorded for at