Gaw A J, Bevan J A
Department of Pharmacology, University of Vermont, College of Medicine, Burlington 05405-0068.
Stroke. 1993 Jan;24(1):105-9; discussion 109-10. doi: 10.1161/01.str.24.1.105.
The flow-induced relaxation of a branch of the rabbit middle cerebral artery was examined to determine if an endothelial-independent as well as -dependent component occurs in pial as well as systemic small arteries and the possible role of products of the cyclooxygenase and the L-arginine nitric oxide synthase pathways.
Intraluminal flow was achieved by the infusion of a tissue bath solution into isometrically mounted rabbit pial arteries in a resistance artery myograph through a small pipette.
Intraluminal flow caused relaxation of the artery segment precontracted with 10 microM histamine. Treatment of endothelium-intact vessels with the nitric oxide synthase inhibitors NG-nitro-L-arginine (L-NNA) (100 microM) or NG-nitro-L-arginine methyl ester (L-NAME) (0.3 mM) significantly reduced the relaxation at flow rates of 5-30 microliters/min. This effect was partially reversed by 1 mM L-arginine. These inhibitors had no effect on the flow-induced relaxation of endothelium-denuded vessels. L-NNA did not influence the relaxation to 1 and 3 microM papaverine. Exposure to 10 microM aspirin, 10 microM indomethacin, or 300 nM tetrodotoxin had no effect on the flow-induced relaxation of either endothelium-intact or -denuded vessels (n = 6). Flow-induced relaxation was attenuated, but not abolished, by removal of the cerebrovascular endothelium. This reduction was not statistically significant.
These results show that intraluminal flow caused relaxation of a branch of the rabbit middle cerebral artery, in part through a mechanism sensitive to inhibitors of nitric oxide synthase, most likely the generation of nitric oxide from the vascular endothelium. The major component of the relaxant response is independent of the endothelium and of nitric oxide synthesis through an L-NNA- or L-NAME-sensitive mechanism. The relaxation does not involve cyclooxygenase products nor neurogenic mediators. These results suggest that pial arteries, like those of the rabbit ear, exhibit a novel mechanism for the flow-induced relaxation of agonist-induced tone that is intrinsic to the tissues of the vascular wall subjacent to the endothelium.
研究兔大脑中动脉分支的血流诱导舒张，以确定软脑膜及全身小动脉中是否存在内皮非依赖性及依赖性成分，以及环氧化酶和L-精氨酸一氧化氮合酶途径产物的可能作用。
通过一根小移液管将组织浴溶液注入阻力动脉肌动描记器中等长安装的兔软脑膜动脉内，以实现管腔内血流。
管腔内血流使预先用10微摩尔组胺预收缩的动脉段舒张。用一氧化氮合酶抑制剂NG-硝基-L-精氨酸（L-NNA）（100微摩尔）或NG-硝基-L-精氨酸甲酯（L-NAME）（0.3毫摩尔）处理内皮完整的血管，在流速为5 - 30微升/分钟时显著降低舒张反应。1毫摩尔L-精氨酸可部分逆转此效应。这些抑制剂对去内皮血管的血流诱导舒张无影响。L-NNA不影响对1和3微摩尔罂粟碱的舒张反应。暴露于10微摩尔阿司匹林、10微摩尔吲哚美辛或300纳摩尔河豚毒素对内皮完整或去内皮血管的血流诱导舒张均无影响（n = 6）。去除脑血管内皮后，血流诱导舒张减弱但未消除。这种降低无统计学意义。
这些结果表明，管腔内血流使兔大脑中动脉分支舒张，部分是通过对一氧化氮合酶抑制剂敏感的机制，很可能是血管内皮产生一氧化氮。舒张反应的主要成分不依赖于内皮，且通过L-NNA或L-NAME敏感机制不依赖于一氧化氮合成。舒张不涉及环氧化酶产物或神经源性介质。这些结果表明，软脑膜动脉与兔耳动脉一样，表现出一种新的机制，即对激动剂诱导张力的血流诱导舒张，这是内皮下方血管壁组织固有的。
