AMILORIDE-SENSITIVE NA+ PATHWAYS IN CAPILLARY ENDOTHELIAL-CELL SWELLING DURING HEMORRHAGIC-SHOCK
AMILORIDE-SENSITIVE NA+ PATHWAYS IN CAPILLARY ENDOTHELIAL-CELL SWELLING DURING HEMORRHAGIC-SHOCK
复制标题
DOI：
10.1152/jappl.1992.73.4.1467
复制
发表时间：
1992-10-01
影响因子：
3.3
通讯作者：
ARFORS, KE
中科院分区：
文献类型：
--
作者：
MAZZONI, MC;INTAGLIETTA, M;ARFORS, KE
我们最近发现，在失血性休克引起的低流量缺血情况下，骨骼肌毛细血管内皮会肿胀。由于缺氧细胞肿胀归因于钠离子和水的内流，本研究旨在确定与这种肿胀相关的钠离子跨膜途径。在最初的一系列实验中，将能阻断多种钠离子通道的氨氯吡嗪（5毫克/千克体重）在休克（40%单次放血）前30分钟静脉注入麻醉的兔子体内。对兔子薄肌中经过处理的毛细血管进行活体显微镜观察显示，在1小时休克期后，内皮细胞没有肿胀，这通过穿过毛细血管的红细胞宽度没有可测量的变化得以证明。相比之下，未经处理的毛细血管内皮肿胀使管腔直径减少了20 - 25%，而基膜保持静止。用氨氯吡嗪类似物研究了氨氯吡嗪对钠离子转运的具体作用。用0.5毫克/千克剂量的5 -（N - N -六亚甲基）氨氯吡嗪（一种钠离子 - 氢离子活性的选择性抑制剂）对动物进行预处理，并没有显著减轻休克引起的肿胀，然而，1毫克/千克的剂量则完全阻止了肿胀。苯甲酰胺（一种钠离子通道电导的选择性抑制剂）即使在0.5毫克/千克的有效剂量下，也不影响肿胀。这些结果表明，在失血性休克期间，钠离子 - 氢离子交换在内皮细胞肿胀中起主要作用，可能是作为一种调节细胞pH值的手段，在缺血期间细胞pH值可能会变酸。具有升高的液压阻力的变窄的毛细血管可能会延迟和减少休克复苏时微循环血流的恢复。
We recently discovered that the endothelium of skeletal muscle capillaries swells in the low-flow ischemia induced by hemorrhagic shock. The present study was undertaken to determine the Na+ transmembrane pathways involved in this swelling, since hypoxic cell swelling is attributed to an influx of Na+ and water. In an initial series of experiments, amiloride (5 mg/kg body wt), which blocks multiple Na+ pathways, was infused intravenously into anesthetized rabbits 30 min prior to shock (40% single-withdrawal hemorrhage). Intravital microscopy of treated capillaries in the rabbit tenuissimus muscle showed that after a 1-h shock period, there was no endothelial cell swelling, as evidenced by no measurable change in the width of red blood cells traversing the capillary. In contrast, the swollen endothelium of untreated capillaries reduced the luminal diameter by 20-25% with a preserved stationary abluminal membrane. The specific effects of amiloride on Na+ transport were investigated with amiloride analogues. Animal pretreatment with 5-(NN-hexamethylene)amiloride, a selective inhibitor of Na+-H+ activity, in a dose of 0.5 mg/kg did not significantly mitigate shock-induced swelling, however, a dose of 1 mg/kg completely prevented it. Phenamil, a selective inhibitor of Na+ channel conductance, even at a potent dosage of 0.5 mg/kg, did not affect swelling. These results suggest a primary role for Na+-H+ exchange in endothelial cell swelling during hemorrhagic shock, possibly as a means to regulate cellular pH, which may become acidic during ischemia. Narrowed capillaries with elevated hydraulic resistances could delay and diminish resumption of microcirculatory flow on shock resuscitation.