Maktabi M A, Faraci F M
Department of Anesthesia, University of Iowa College of Medicine, Iowa City 52242.
Stroke. 1994 Jul;25(7):1489-93; discussion 1494. doi: 10.1161/01.str.25.7.1489.
The choroid plexus, the major source of cerebrospinal fluid (CSF), contains receptors for angiotensin II and a very high concentration of angiotensin converting enzyme. Circulating angiotensin II decreases blood flow to the choroid plexus and the production of CSF. During recovery from hypoxia, marked increases in circulating angiotensin II have been described in some studies. We tested the hypothesis that CSF production decreases during posthypoxemic reoxygenation and examined related changes in plasma concentrations of angiotensin II. We also determined whether effect of posthypoxic reoxygenation on production of CSF is due to endogenous release of angiotensin II.
We measured production of CSF in chloralose-anesthetized rabbits using ventriculocisternal perfusion of artificial CSF containing blue dextran. After control measurements, rabbits were subjected to one of the following interventions: (1) 30 minutes of hypoxia (PaO2 = 36 +/- 1 mmHg [mean +/- SE]) followed by 90 minutes of reoxygenation; (2) 30 minutes of hypoxia (PaO2 = 37 +/- 2 mmHg) followed by 90 minutes of reoxygenation in the presence of the angiotensin II antagonist saralasin; (3) hypoxia for 120 minutes (PaO2 = 35 +/- 1 mmHg); and (4) infusion of vehicle under normoxic conditions for 120 minutes (time control). Plasma concentrations of angiotensin II were also measured (radioimmunoassay) under control conditions, during hypoxia, and during posthypoxic reoxygenation (first intervention) and at corresponding time intervals in time control animals (fourth intervention).
Under control conditions, the rate of production of CSF averaged 6.7 +/- 0.1 microL.min-1. During posthypoxemic reoxygenation, production of CSF decreased by 31 +/- 4% (P < .05). In the presence of sarlasin, CSF production did not change significantly during posthypoxemic reoxygenation (-12 +/- 6%, P > .05). In time control animals and during prolonged hypoxia, CSF production did not change significantly (-12 +/- 5% [P > .05] and 9 +/- 7% [P > .05], respectively). Plasma concentrations of angiotensin were below the threshold of sensitivity of the assay under control conditions and during interventions in animals that were made hypoxic and then reoxygenated and in time control animals.
CSF production decreases during posthpoxemic reoxygenation. Since plasma concentrations of angiotensin II did not change during posthypoxic reoxygenation, this effect does not appear to be mediated by increases in circulating angiotensin II. We speculate that endogenous release of angiotensin II, perhaps in the choroid plexus epithelium, decreases production of CSF after hypoxic brain injury.
脉络丛是脑脊液（CSF）的主要来源，含有血管紧张素II受体和高浓度的血管紧张素转换酶。循环中的血管紧张素II会减少脉络丛的血流量和脑脊液生成。在缺氧恢复过程中，一些研究描述了循环中血管紧张素II的显著增加。我们检验了以下假设：低氧后复氧期间脑脊液生成减少，并研究了血管紧张素II血浆浓度的相关变化。我们还确定了低氧后复氧对脑脊液生成的影响是否归因于血管紧张素II的内源性释放。
我们使用含蓝色葡聚糖的人工脑脊液进行脑室池灌注，测量水合氯醛麻醉的家兔的脑脊液生成。在对照测量后，家兔接受以下干预之一：（1）30分钟缺氧（动脉血氧分压[PaO2]=36±1mmHg[平均值±标准误]），随后90分钟复氧；（2）30分钟缺氧（PaO2=37±2mmHg），随后在血管紧张素II拮抗剂沙拉新存在的情况下进行90分钟复氧；（3）120分钟缺氧（PaO2=35±1mmHg）；（4）在常氧条件下输注溶媒120分钟（时间对照）。还在对照条件下、缺氧期间、低氧后复氧期间（首次干预）以及时间对照动物（第四次干预）的相应时间间隔测量血管紧张素II的血浆浓度（放射免疫测定）。
在对照条件下，脑脊液生成速率平均为6.7±0.1μL·min-1。在低氧后复氧期间，脑脊液生成减少31±4%（P<.05）。在沙拉新存在的情况下，低氧后复氧期间脑脊液生成无显著变化（-12±6%，P>.05）。在时间对照动物和长时间缺氧期间，脑脊液生成无显著变化（分别为-12±5%[P>.05]和9±7%[P>.05]）。在对照条件下以及在低氧后复氧的动物和时间对照动物的干预期间，血管紧张素的血浆浓度低于测定的灵敏度阈值。
低氧后复氧期间脑脊液生成减少。由于低氧后复氧期间血管紧张素II的血浆浓度未发生变化，这种效应似乎不是由循环中血管紧张素II的增加介导的。我们推测血管紧张素II的内源性释放，可能在脉络丛上皮中，在缺氧性脑损伤后会减少脑脊液生成。
