Maktabi M A, Todd M M, Stachovic G
Department of Anesthesia, University of Iowa College of Medicine, Iowa City 52242, USA.
Stroke. 1995 Oct;26(10):1871-6. doi: 10.1161/01.str.26.10.1871.
and Purpose Hypoxia increases cerebral blood flow (CBF). Hypoxia also exerts a major influence on the renin-angiotensin system. In addition to the circulating renin-angiotensin system, a local renin-angiotensin system appears to be present in the brain, and angiotensin II receptors have been identified in cerebral blood vessels. In this study we tested the hypothesis that endogenous angiotensin II attenuates dilatation of the cerebral vessels during hypoxia.
Pentobarbital-anesthetized rabbits were prepared for measurement of blood flow (microspheres) and assigned to one of two groups: in group 1 (n = 11), rabbits were subjected to 30 minutes of stable hypoxia (PaO2 = 34 +/- 1 mm Hg, mean +/- SD) followed by 15 minutes of reoxygenation (PaO2 = 177 to 200 mm Hg). Blood flow was measured four times: under control conditions, after 15 and 30 minutes of hypoxia, and after 15 minutes of reoxygenation. This was a control group to characterize changes in CBF during hypoxia. In group 2 (n = 11), blood flow was measured as in the previous group except that an infusion of the angiotensin II receptor antagonist saralasin (1 microgram.kg-1.min-1 IV) was started with the onset of hypoxia and continued through reoxygenation to the end of the experiment. The goal of this group was to examine whether endogenous activation of receptors for angiotensin II influences increases in CBF during hypoxia. In a separate series of experiments we examined the influence of the angiotensin-converting enzyme (ACE) inhibitor captopril on the hypoxic response. Thus, in one group of rabbits we measured CBF in the same manner as in group 1 (n = 13). In another group of rabbits we also measured blood flow as in group 1 except that rabbits received 10 mg/kg of the ACE inhibitor captopril before the control measurement (n = 11). We tested for significant differences between groups using two-way ANOVA.
Under control conditions, CBF was similar in all groups and averaged 53 +/- 15 mL.min-1.100 g-1. During hypoxia, CBF increased to a greater extent in the absence versus the presence of saralasin (95 +/- 31 and 104 +/- 30 mL.min-1.100 g-1 versus 72 +/- 24 and 71 +/- 25 mL.min-1.100 g-1, respectively; P = .003). Increase in CBF during hypoxia was also significantly greater in the animals that did not receive captopril versus those that were treated with captopril (100 +/- 24 and 89 +/- 16 mL.min-1.100 g-1 versus 72 +/- 16 and 73 +/- 17 mL.min-1.100 g-1). To rule out the possibility that saralasin produced non-specific attenuation of cerebral vasodilatation, we tested the influence of hypercapnia on CBF in the absence and presence of saralasin. During normocapnia, CBF values were not significantly different in the absence and presence of saralasin (57 +/- 17 and 64 +/- 6 mL.min-1.100 g-1, respectively; P > .05). Hypercapnia increased CBF similarly in the absence and presence of saralasin (81 +/- 22 and 91 +/- 19 mL.min-1.100 g-1; PaCO2 = 61 +/- 2 and 60 +/- 2 mm Hg, respectively; P > .05).
Because the ACE inhibitor captopril and the angiotensin II receptor blocker saralasin attenuated increased in CBF during hypoxia, the findings suggest that endogenous release of angiotensin II contributes to the increase in CBF during hypoxia.
缺氧可增加脑血流量（CBF）。缺氧对肾素 - 血管紧张素系统也有重大影响。除了循环中的肾素 - 血管紧张素系统外，脑内似乎还存在局部肾素 - 血管紧张素系统，并且在脑血管中已鉴定出血管紧张素II受体。在本研究中，我们检验了内源性血管紧张素II在缺氧期间减弱脑血管扩张的假说。
将戊巴比妥麻醉的家兔准备好用于测量血流量（微球法），并分为两组：在第1组（n = 11）中，家兔经历30分钟的稳定缺氧（动脉血氧分压（PaO2）= 34±1 mmHg，平均值±标准差），随后进行15分钟的复氧（PaO2 = 177至200 mmHg）。血流量测量4次：在对照条件下、缺氧15分钟和30分钟后以及复氧15分钟后。这是一个对照组，用于表征缺氧期间CBF的变化。在第2组（n = 11）中，血流量的测量方法与前一组相同，不同之处在于从缺氧开始时就开始静脉输注血管紧张素II受体拮抗剂沙拉新（1μg·kg-1·min-1），并持续至复氧结束及实验结束。该组的目的是研究血管紧张素II受体的内源性激活是否影响缺氧期间CBF的增加。在另一系列实验中，我们研究了血管紧张素转换酶（ACE）抑制剂卡托普利对缺氧反应的影响。因此，在一组家兔中，我们以与第1组相同的方式测量CBF（n = 13）。在另一组家兔中，我们也以与第1组相同的方式测量血流量，不同之处在于家兔在对照测量前接受10 mg/kg的ACE抑制剂卡托普利（n = 11）。我们使用双向方差分析检验组间的显著差异。
在对照条件下，所有组的CBF相似，平均为53±15 mL·min-1·100 g-1。在缺氧期间，与存在沙拉新相比，不存在沙拉新时CBF增加的幅度更大（分别为95±31和104±30 mL·min-1·100 g-1 与72±24和71±25 mL·min-1·100 g-1；P = 0.003）。在缺氧期间，未接受卡托普利治疗的动物与接受卡托普利治疗的动物相比，CBF的增加也显著更大（100±24和89±16 mL·min-1·100 g-1 与72±16和73±17 mL·min-1·100 g-1）。为排除沙拉新产生脑血管扩张非特异性减弱的可能性，我们测试了在不存在和存在沙拉新的情况下高碳酸血症对CBF的影响。在正常碳酸血症期间，不存在和存在沙拉新时的CBF值无显著差异（分别为57±17和64±6 mL·min-1·100 g-1；P>0.05）。在不存在和存在沙拉新的情况下，高碳酸血症使CBF增加的情况相似（81±22和91±19 mL·min-1·
