DITHIONITE INCREASES RADICAL FORMATION AND DECREASES VASOCONSTRICTION IN THE LUNG - EVIDENCE THAT DITHIONITE DOES NOT MIMIC ALVEOLAR HYPOXIA
DITHIONITE INCREASES RADICAL FORMATION AND DECREASES VASOCONSTRICTION IN THE LUNG - EVIDENCE THAT DITHIONITE DOES NOT MIMIC ALVEOLAR HYPOXIA
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DOI：
10.1161/01.res.77.1.174
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发表时间：
1995-07-01
影响因子：
20.1
通讯作者：
WEIR, EK
中科院分区：
文献类型：
--
作者：
ARCHER, SL;HAMPL, V;WEIR, EK
二硫代盐是一种强大的还原剂，用于体外脱氧血红蛋白和创造厌氧条件。近年来，在研究肺循环和颈动脉体中O-2传感器的实验中，二亚铁酸盐被用作制造“缺氧”的便捷手段。我们评估了低氧通气造成的缺氧和二亚砜造成的缺氧对肺循环的影响不同的假设。在体外，将二亚铁(10（-5)~ 10(-3)mol/L）加入到氧化的Krebs溶液中，快速生成超氧阴离子，并呈剂量依赖性。亚硫代盐消耗O-2的同时产生超氧自由基，两个过程都在几秒钟内达到峰值。缺氧只有在O-2再补给被阻止的情况下才能维持。在离体大鼠肺（无论是自体血液灌注还是克雷布斯溶液灌注）中，在缺氧性肺血管收缩发生之前，单靠低氧通气将灌注PO2从大约降低到140至40 mm Hg，并通过鲁米诺增强化学发光测量降低肺活性氧（AOS）水平。对血管紧张素II和KCl的收缩反应没有因间歇性缺氧而受损，肺重量也没有增加。相反，二亚砜损害了克雷布斯溶液灌注肺对所有血管收缩剂的收缩反应，并增加了肺重量。在常氧通气时，二亚硫铵给药（5x10(-3) mol/L）到肺动脉，不会引起血管收缩，只会短暂降低PO2（因为肺泡不断地再供给O-2）。当与低氧通气叠加时，二亚硫铵进一步将PO2从大约40降低到大约0 mm Hg，并引起额外的收缩。与低氧通气不同，二亚硫铵增加了AOS的产生。抗氧化酶可减少二硫代盐诱导的自由基产生，减轻血管反应性丧失和肺水肿。综上所述，与低氧通气不同，二亚硝酸盐通过产生超氧阴离子和过氧化氢导致肺部水肿和血管反应性丧失。二亚硫磷引起的缺氧不等同于真正的缺氧，因为必须伴有AOS的产生，二亚硫磷的使用不应取代真正的缺氧。O-2传感研究
Dithionite is a powerful reducing agent used to deoxygenate hemoglobin and create anaerobic conditions in vitro. Recently, dithionite has been used as a convenient means of creating ''hypoxia'' in experiments studying the O-2 sensor in the pulmonary circulation and carotid body. We evaluated the hypothesis that hypoxia created by hypoxic ventilation and that created by dithionite have different effects on the pulmonary circulation. In vitro, dithionite (10(-5) to 10(-3) mol/L), added to oxygenated Krebs' solution, rapidly created superoxide anion in a dose-dependent manner. Dithionite consumed O-2 in parallel with the generation of superoxide radical, with both processes peaking within seconds. Anoxia was sustained only if resupply of O-2 was prevented. In isolated rat lungs (whether perfused with autologous blood or Krebs' solution), hypoxic ventilation alone lowered perfusate PO2 from approximate to 140 to 40 mm Hg and decreased lung levels of activated oxygen species (AOS), measured by luminol-enhanced chemiluminescence, before the onset of hypoxic pulmonary vasoconstriction. Constrictor responses to angiotensin II and KCl were not impaired by intermittent hypoxic challenges, and lung weight did not increase. In contrast, dithionite impaired constrictor responses of the Krebs' solution-perfused lungs to all vasoconstrictors tested and increased lung weight. When given as a bolus (5x10(-3) mol/L) into the pulmonary artery during normoxic ventilation, dithionite caused no vasoconstriction and only briefly lowered PO2 (because of constant resupply of O-2 from the alveoli). When superimposed on hypoxic ventilation, dithionite further lowered PO2 from approximate to 40 to approximate to 0 mm Hg and caused additional constriction, Unlike hypoxic ventilation, dithionite increased AOS production. Antioxidant enzymes diminished dithionite-induced radical production and diminished the Loss of vascular reactivity and lung edema. In conclusion, unlike hypoxic ventilation, dithionite causes edema and loss of vascular reactivity in the lung by generating superoxide anion and hydrogen peroxide. Hypoxia elicited by dithionite is not equivalent to authentic hypoxic because of the obligatory associated generation of AOS, Dithionite usage should not be substituted for authentic hypoxia. in studies of O-2 sensing.