Wei E P, Kukreja R, Kontos H A
Department of Medicine, Medical College of Virginia, Richmond 23298.
Stroke. 1992 Nov;23(11):1623-8; discussion 1628-9. doi: 10.1161/01.str.23.11.1623.
We investigated the chemical identity of the endothelium-derived relaxing factor generated by acetylcholine in cerebral microvessels by studying the effects and mechanism of action of inhibitors of nitric oxide synthesis from arginine on the vasodilation and endothelium-derived relaxing factor production induced by topical application of acetylcholine in cerebral arterioles.
We determined cerebral arteriolar dilation and endothelium-derived relaxing factor production by bioassay in anesthetized cats equipped with cranial windows during superfusion of 10(-7) M acetylcholine before and after administration of either NG-monomethyl L-arginine or NG-nitro-L-arginine, two inhibitors of nitric oxide synthesis.
NG-Nitro-L-arginine abolished the vasodilation from acetylcholine and eliminated the production of endothelium-derived relaxing factor in the bioassay experiments. NG-Monomethyl L-arginine had no effect on the response to acetylcholine in the absence of pretreatment. However, after pretreatment with the detergent sodium dodecyl sulfate to increase cell membrane permeability, the inhibitor had effects identical to those of NG-nitro-L-arginine. L-Arginine reversed the effects of the inhibitors of nitric oxide synthesis. Neither inhibitor affected baseline vascular caliber, nor did they generate a vasoconstrictor agent in the bioassay experiments. The two inhibitors of nitric oxide synthesis did not affect the response to nitroprusside or adenosine, showing that the effect on responses to acetylcholine was specific. Also, the blockade of the response to acetylcholine induced by the inhibitors of nitric oxide synthesis was unaffected by treatment with superoxide dismutase and catalase, showing that the effect was not mediated by oxygen radicals.
The endothelium-derived relaxing factor generated by acetylcholine in cerebral arterioles of cats is either nitric oxide or a nitric oxide-containing substance. The effect of these inhibitors on the response to acetylcholine is mediated by inhibition of the synthesis of nitric oxide. There is no involvement of radicals, and no vasoconstrictor agent is generated.
我们通过研究精氨酸一氧化氮合成抑制剂对脑微动脉局部应用乙酰胆碱诱导的血管舒张和内皮源性舒张因子产生的作用及作用机制，来探究脑微血管中由乙酰胆碱产生的内皮源性舒张因子的化学特性。
在配备颅窗的麻醉猫中，于灌注10(-7) M乙酰胆碱前后，分别给予一氧化氮合成抑制剂NG-单甲基L-精氨酸或NG-硝基-L-精氨酸，通过生物测定法测定脑微动脉舒张和内皮源性舒张因子的产生。
在生物测定实验中，NG-硝基-L-精氨酸消除了乙酰胆碱引起的血管舒张，并消除了内皮源性舒张因子的产生。在未进行预处理时，NG-单甲基L-精氨酸对乙酰胆碱的反应无影响。然而，在用去污剂十二烷基硫酸钠预处理以增加细胞膜通透性后，该抑制剂产生了与NG-硝基-L-精氨酸相同的作用。L-精氨酸逆转了一氧化氮合成抑制剂的作用。两种抑制剂均未影响基线血管管径，在生物测定实验中也未产生血管收缩剂。这两种一氧化氮合成抑制剂对硝普钠或腺苷的反应无影响，表明其对乙酰胆碱反应的影响具有特异性。此外，一氧化氮合成抑制剂诱导的对乙酰胆碱反应的阻断不受超氧化物歧化酶和过氧化氢酶处理的影响，表明该作用不是由氧自由基介导的。
猫脑微动脉中由乙酰胆碱产生的内皮源性舒张因子要么是一氧化氮，要么是含一氧化氮的物质。这些抑制剂对乙酰胆碱反应的作用是通过抑制一氧化氮的合成介导的。不存在自由基参与，也未产生血管收缩剂。
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