高葡萄糖浓度通过内皮机制使脑动脉扩张并减弱肌源性张力。

High glucose concentrations dilate cerebral arteries and diminish myogenic tone through an endothelial mechanism.

作者信息

Cipolla M J, Porter J M, Osol G

机构信息

Department of Surgery, Oregon Health Sciences University, Portland.

出版信息

Stroke. 1997 Feb;28(2):405-10; discussion 410-1. doi: 10.1161/01.str.28.2.405.

DOI:10.1161/01.str.28.2.405

PMID:9040698

Abstract

BACKGROUND AND PURPOSE

Diabetes is associated with cerebrovascular disease and impaired autoregulation of cerebral blood flow. The purpose of this study was to determine the effect of acute glucose exposure on basal tone and myogenic reactivity of isolated rat cerebral arteries.

METHODS

Posterior cerebral arteries (PCAs, n = 38) were dissected from male Wistar rats and mounted on glass cannulas in a system that allowed control of transmural pressure (TMP) and measurement of lumen diameter. Arteries were exposed to various concentrations of glucose, and the amount of basal tone and reactivity to TMP was measured. The effect of elevated glucose on cerebral endothelial modulation of basal tone was determined by mechanical denudation and the use of inhibitors of both nitric oxide and prostaglandin synthesis.

RESULTS

Arteries exposed to 44 versus 5.5 mmol/L glucose developed significantly less intrinsic tone (percent tone, 2 +/- 1% versus 28 +/- 2%; P < .01) and responded passively to increases in TMP. Preexisting tone present in 5.5 mmol/L glucose was eliminated on exposure to 44 mmol/L glucose, which decreased tone from 30 +/- 5% to 5 +/- 4% (P < .01). Glucose-induced dilations were concentration dependent such that half-maximal responses were obtained at 25 +/- 2 mmol/L. Endothelial removal abolished this effect, and the amount of tone was similar in 5.5 versus 44 mmol/L glucose (percent tone, 46 +/- 6% versus 49 +/- 5%; P > .05), as did inhibition of nitric oxide production with 0.3 mmol/L nitro-L-arginine (percent tone, 52 +/- 4% versus 46 +/- 3%; P > .05); however, blockade of the cyclooxygenase pathway with indomethacin (10(-5) mmol/L) only partially inhibited the dilation to glucose (percent tone, 32 +/- 3% in 5.5 mmol/L versus 12.4 +/- 3% in 44 mmol/L; P < .01).

CONCLUSIONS

Acute glucose exposure dilates arteries with intrinsic tone and impairs cerebrovascular reactivity to TMP via an endothelium-mediated mechanism that involves nitric oxide and prostaglandins.

摘要

背景与目的

糖尿病与脑血管疾病及脑血流自身调节受损有关。本研究旨在确定急性葡萄糖暴露对离体大鼠脑动脉基础张力和肌源性反应性的影响。

方法

从雄性Wistar大鼠分离出大脑后动脉（PCA，n = 38），并安装在玻璃插管上，置于一个可控制跨壁压力（TMP）并测量管腔直径的系统中。将动脉暴露于不同浓度的葡萄糖中，测量基础张力和对TMP的反应性。通过机械剥脱以及使用一氧化氮和前列腺素合成抑制剂来确定高血糖对脑内皮基础张力调节的影响。

结果

与暴露于5.5 mmol/L葡萄糖相比，暴露于44 mmol/L葡萄糖的动脉产生的固有张力明显更低（张力百分比，2±1% 对28±2%；P <.01），并且对TMP升高呈被动反应。暴露于44 mmol/L葡萄糖时，5.5 mmol/L葡萄糖中存在的先前张力被消除，张力从30±5%降至5±4%（P <.01）。葡萄糖诱导的舒张呈浓度依赖性，在25±2 mmol/L时获得半数最大反应。内皮去除消除了这种效应，5.5 mmol/L和44 mmol/L葡萄糖中的张力大小相似（张力百分比，46±6% 对49±5%；P >.05），用0.3 mmol/L硝基-L-精氨酸抑制一氧化氮生成时也是如此（张力百分比，52±4% 对46±3%；P >.05）；然而，用吲哚美辛（10(-5) mmol/L）阻断环氧化酶途径仅部分抑制对葡萄糖的舒张（5.5 mmol/L时张力百分比为32±3%，44 mmol/L时为12.4±3%；P <.01）。