短期低氧和高碳酸血症对仔猪N-甲基-D-天冬氨酸诱导的脑血管舒张的不同影响。

Differential effects of short-term hypoxia and hypercapnia on N-methyl-D-aspartate-induced cerebral vasodilatation in piglets.

作者信息

Bari F, Errico R A, Louis T M, Busija D W

机构信息

Departments of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1083, USA.

出版信息

Stroke. 1996 Sep;27(9):1634-9; discussion 1639-40. doi: 10.1161/01.str.27.9.1634.

DOI:10.1161/01.str.27.9.1634

PMID:8784141

Abstract

BACKGROUND AND PURPOSE

Recent studies in piglets show that either asphyxia or global cerebral ischemia, which combines effects of hypoxia and hypercapnia, transiently attenuates N-methyl-D-aspartate (NMDA)-induced pial arteriolar dilation. The purpose of this study was to determine individually the effects of hypoxic hypoxia and normoxic hypercapnia on NMDA-dependent cerebrovascular reactivity. In addition, we examined mechanisms involved in reduced cerebral vascular dilation to NMDA.

METHODS

In anesthetized piglets, we examined pial arteriolar diameters using a cranial window and intravital microscopy. Arteriolar responses to topically applied NMDA were determined under control conditions and after arterial hypoxia or arterial hypercapnia. In addition, arteriolar responses to NMDA were examined in animals given indomethacin (10 mg/kg IV) or superoxide dismutase (100 U/mL, topical application) before hypoxia.

RESULTS

Under control conditions, application of NMDA produced a dose-related dilation of pial arterioles (eg, 9 +/- 1% to 10(-5), 15 +/- 2% to 5 x 10(-5), and 28 +/- 5% to 10(-4) mol/L NMDA above baseline, respectively, in the hypoxic group; n = 6, P < .05). After transient exposure to 15 minutes of hypoxic hypoxia, arteriolar responses to NMDA were reduced at 30 minutes and at 60 minutes (10(-4) mol/L NMDA dilated by 12 +/- 5% and 18 +/- 5%, respectively; n = 6, P < .05). Five minutes of hypoxic hypoxia also reduced dilatation to NMDA. Indomethacin or superoxide dismutase preserved arteriolar responses to NMDA after 15 minutes of hypoxia. Pial arteriolar responses to NMDA remained unimpaired during and after hypercapnia.

CONCLUSIONS

Short-term severe hypoxic hypoxia and reventilation impair the NMDA-induced dilatation of pial arterioles. Respiratory acidosis alone does not modify pial arteriolar reactivity to NMDA. The reduced responsiveness of the cerebral blood vessels to NMDA caused by hypoxia appears to be due to action of oxygen radicals.

摘要

背景与目的

最近在仔猪身上进行的研究表明，窒息或全脑缺血（其结合了缺氧和高碳酸血症的影响）会短暂减弱N-甲基-D-天冬氨酸（NMDA）诱导的软脑膜小动脉扩张。本研究的目的是分别确定低氧性缺氧和常氧性高碳酸血症对NMDA依赖性脑血管反应性的影响。此外，我们研究了脑血管对NMDA扩张反应减弱所涉及的机制。

方法

在麻醉的仔猪中，我们使用颅骨开窗和活体显微镜检查软脑膜小动脉直径。在对照条件下以及动脉缺氧或动脉高碳酸血症后，确定小动脉对局部应用NMDA的反应。此外，在缺氧前给予吲哚美辛（10mg/kg静脉注射）或超氧化物歧化酶（100U/mL，局部应用）的动物中，检查小动脉对NMDA的反应。

结果

在对照条件下，应用NMDA会使软脑膜小动脉产生剂量相关的扩张（例如，在缺氧组中，相对于基线，10⁻⁵mol/L NMDA使小动脉扩张9±1%，5×10⁻⁵mol/L使小动脉扩张15±2%，10⁻⁴mol/L使小动脉扩张28±5%；n = 6，P <.05）。短暂暴露于15分钟的低氧性缺氧后，在30分钟和60分钟时小动脉对NMDA的反应减弱（10⁻⁴mol/L NMDA分别使小动脉扩张12±5%和18±5%；n = 6，P <.05）。5分钟的低氧性缺氧也会减弱对NMDA的扩张反应。吲哚美辛或超氧化物歧化酶在缺氧15分钟后可保留小动脉对NMDA的反应。在高碳酸血症期间及之后，软脑膜小动脉对NMDA的反应保持未受损害。