ROLE OF ENDOTHELIUM-DERIVED RELAXING FACTOR IN CEREBRAL-CIRCULATION - LARGE ARTERIES VS MICROCIRCULATION
ROLE OF ENDOTHELIUM-DERIVED RELAXING FACTOR IN CEREBRAL-CIRCULATION - LARGE ARTERIES VS MICROCIRCULATION
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DOI：
10.1152/ajpheart.1991.261.4.h1038
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发表时间：
1991-10-01
影响因子：
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通讯作者：
FARACI, FM
中科院分区：
文献类型：
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作者：
FARACI, FM
本研究检验了脑内内皮源性松弛因子（EDRF）的形成对大动脉基底张力的影响大于小动脉基底张力的假设。麻醉大鼠通过颅窗测量颅底动脉及其分支直径和大脑小动脉直径。在对照条件下，局部应用N(G)-单甲基- l-精氨酸（L-NMMA）可以抑制l-精氨酸生成EDRF或一氧化氮（NO），产生与初始血管直径相关的浓度相关的收缩。10(-5) M L-NMMA使大动脉[直径= 275 +/- 10 μ M（平均值+/- SE）]收缩10.4 +/- 0.8%。相比之下，无论脑区如何，小动脉（62 +/- 6 mu-m）仅收缩3.7 +/- 0.6%（与大动脉相比P < 0.01）。U-46619对大动脉和小动脉产生类似的收缩，这表明小动脉对L-NMMA的反应降低不是由于收缩能力受损。硝普钠对大动脉和小动脉产生类似的扩张，这表明小血管中鸟苷酸环化酶的活性没有降低。L-NMMA可抑制大动脉和小动脉对乙酰胆碱的扩张反应，但不抑制硝普塞。由此可见，由l -精氨酸合成EDRF会影响脑血管的基底张力，且对大动脉的影响最大。相反，EDRF或NO在脑循环中介导对乙酰胆碱的反应中的作用在大动脉和微循环中是相似的。
This study examined the hypothesis that formation of endothelium-derived relaxing factor (EDRF) in the brain has a greater influence on basal tone in large arteries than arterioles. Diameters of the basilar artery and its branches and of arterioles on the cerebrum were measured through cranial windows in anesthetized rats. Under control conditions, topical application of N(G)-monomethyl-L-arginine (L-NMMA), which inhibits formation of EDRF or nitric oxide (NO) from L-arginine, produced concentration-related constriction that was dependent on initial vessel diameter. Large arteries [diameter = 275 +/- 10-mu-m (means +/- SE)] constricted by 10.4 +/- 0.8% in response to 10(-5) M L-NMMA. In contrast, arterioles (62 +/- 6-mu-m) constricted by only 3.7 +/- 0.6% (P < 0.01 vs. large arteries), regardless of brain region. U-46619 produced similar constriction of large arteries and arterioles, which indicates that reduced responses to L-NMMA in arterioles is not due to impaired constrictor capacity. Sodium nitroprusside produced similar dilatation of large arteries and arterioles, which suggests that activity of guanylate cyclase is not reduced in small vessels. Dilator responses of large arteries and arterioles to acetylcholine, but not nitroprusside, were inhibited by L-NMMA. Thus synthesis of EDRF from L-arginine influences basal tone of cerebral blood vessels, and the effect is greatest in large arteries. In contrast, the role of EDRF or NO in mediating responses to acetylcholine in the cerebral circulation is similar in large arteries and the microcirculation.