The Effect of Endothelin-1 on Alveolar Fluid Clearance and Pulmonary Edema Formation in the Rat
The Effect of Endothelin-1 on Alveolar Fluid Clearance and Pulmonary Edema Formation in the Rat
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DOI：
10.1213/ane.0b013e31818881a8
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发表时间：
2009-01-01
影响因子：
5.7
通讯作者：
Mairbaeurl, Heimo
中科院分区：
文献类型：
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作者：
Berger, Marc Moritz;Rozendal, C. Sjula;Mairbaeurl, Heimo
背景：内皮素-1（ET-1）被认为在肺水肿的形成中起关键作用。潜在的机制仍然不确定，但可能包括毛细血管压力和血管通透性的改变。没有研究调查ET-1是否也影响肺泡液体清除，肺泡液体清除是肺水肿消退的主要机制。因此，我们进行了这项研究，以澄清影响的ET-1对肺泡重吸收和液体平衡在rat lung.METHODS：肺泡液体清除率测定在流体滴注大鼠肺使用5%，白蛋白溶液与或不与ET-1（10（-7）M）和/或阿米洛利（100 μ M）。在离体、通气、恒压灌流的大鼠肺模型上，测定了有或无ET-1时的肺泡液体平衡、肺水肿形成时间、肺毛细血管压力和肺泡白蛋白通透性（0.8 nM）加入到灌注液中。在液体灌注的肺中，ET-1使肺泡液体清除率降低约65%，与阿米洛利敏感性跨上皮Na（+）转运减少有关（P < 0.001）。内皮素B受体拮抗剂BQ 788可完全阻断ET-1的抑制作用（P = 0.006），而内皮素A受体拮抗剂BQ 123则无此作用（P = 0.663）。在离体、通气、灌流的大鼠肺中，ET-1引起约20%的肺泡液体净积聚（11 = 0.011 vs对照），而对照大鼠肺清除约20%的滴注液体。ET-1使肺毛细血管压升高（+9.4cmH2O），肺灌流量减少（-81%），肺重量增加加快，肺存活时间缩短（P < 0.001）。结论：ET-1通过抑制阿米洛利敏感的上皮Na+通道抑制麻醉大鼠肺泡液体清除。ET-1的抑制作用是通过激活内皮素B受体实现的。这些发现提示ET-1除了增加毛细血管压力外，还有助于肺水肿形成的机制。
BACKGROUND: Endothelin-1 (ET-1) is thought to play a pivotal role in pulmonary edema formation. The underlying mechanisms remain uncertain but may include alterations in capillary pressure and vascular permeability. There are no studies investigating whether E T-l also affects alveolar fluid clearance which is the primary mechanism for the resolution Of pulmonary edema. Therefore, we, performed this study to clarify effects of ET-1 on alveolar reabsorption and fluid balance in the rat lung.METHODS: Alveolar fluid clearance was measured in fluid instilled rat lungs using a 5%, albumin Solution with or without ET-1 (10(-7) M) and/or amiloride (100 mu M). Net alveolar fluid balance, time Course of edema formation, pulmonary capillary pressure, and alveolar permeability to albumin were Measured in the isolated, ventilated, constant pressure perfused rat lung with or without ET-1 (0.8 nM) added to the perfusateRESULTS: In the fluid-instilled lung, ET-1 reduced alveolar fluid clearance by about 65%, an effect that was related to a decrease in amiloride-sensitive transepithelial Na(+) transport (P < 0.001). The ET-1-induced inhibition was completely prevented by the endothelin B receptor antagonist BQ788 (P = 0.006), whereas the endothelin A receptor antagonist BQ123 had no effect (P = 0.663). In the isolated, ventilated, perfused rat lung ET-1 Caused a net accumulation of alveolar fluid by about 20%, (11 = 0.011 vs control), whereas lungs of control rats cleared about (20%, of the instilled fluid. ET-1 increased pulmonary capillary pressure (+9.4 cm H(2)O), decreased perfusate flow (-81%), accelerated lung weight gain and reduced lung survival time (P < 0.001). Permeability to albumin was not significantly affected by ET-1 (P = 0.24).CONCLUSION: ET-1 inhibitis alveolar fluid clearance of anesthetized rats by inhibition of amiloride-sensitive epithelial Na(+) channels. The inhibitory effect of ET-1 results from activation of the endothelin B receptor. These findings Suggest a mechanism by which ET-1, in addition to increasing capillary Pressure, contributes to pulmonary edema formation.