Rosenblum W I, Nishimura H, Nelson G H
Department of Pathology (Neuropathology), Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0017.
Am J Physiol. 1992 May;262(5 Pt 2):H1343-9. doi: 10.1152/ajpheart.1992.262.5.H1343.
As previously reported, NG-monomethyl-L-arginine (L-NMMA) constricted pial arterioles, inhibited dilation of pial arterioles by acetylcholine (ACh) or L-arginine (L-Arg), and enhanced platelet adhesion/aggregation at sites of endothelial damage. However, all of these effects were inhibited by local application of 20 micrograms/ml indomethacin (Indo). When 100 micrograms/ml acetylsalicylic acid were used instead of Indo, the acid also blocked the effects of L-NMMA. Superoxide dismutase (SOD; 50 U/ml) blocked the constriction produced by L-NMMA and also blocked the constriction produced by N omega-nitro-L-arginine (NNA). SOD also prevented L-NMMA from blocking dilation by ACh. SOD itself had no effect on diameter or on the response to ACh, norepinephrine, or BaCl2. The effects of L-NMMA and of Indo were also selective. Thus L-NMMA did not inhibit dilation by prostacyclin or bradykinin, and Indo did not inhibit dilation by prostacyclin. Indo did not interfere with the ability of arginase to enhance platelet adhesion/aggregation or with the ability of ACh or L-Arg to inhibit adhesion/aggregation. We conclude that in mouse cerebral microcirculation the ability of L-NMMA and NNA to constrict arterioles, the ability of L-NMMA to inhibit dilation by ACh or L-Arg and the ability of L-NMMA to enhance platelet adhesion/aggregation are all related to interference with phenomena dependent on "classical" endothelium-derived relaxing factor (EDRFACh). However, in this preparation the action of L-NMMA or NNA may not be due to competitive inhibition of the enzyme producing EDRFACh from L-Arg. Rather, L-NMMA and NNA appear to activate cyclooxygenase with resultant production of superoxide, which inactivates EDRFACh.
如先前报道，N-单甲基-L-精氨酸（L-NMMA）可使软脑膜小动脉收缩，抑制乙酰胆碱（ACh）或L-精氨酸（L-Arg）引起的软脑膜小动脉扩张，并增强血小板在内皮损伤部位的黏附/聚集。然而，局部应用20微克/毫升吲哚美辛（Indo）可抑制所有这些效应。当使用100微克/毫升乙酰水杨酸代替Indo时，该酸也可阻断L-NMMA的效应。超氧化物歧化酶（SOD；50单位/毫升）可阻断L-NMMA引起的收缩，也可阻断Nω-硝基-L-精氨酸（NNA）引起的收缩。SOD还可防止L-NMMA阻断ACh引起的扩张。SOD本身对血管直径或对ACh、去甲肾上腺素或BaCl2的反应无影响。L-NMMA和Indo的效应也是选择性的。因此，L-NMMA不抑制前列环素或缓激肽引起的扩张，Indo不抑制前列环素引起的扩张。Indo不干扰精氨酸酶增强血小板黏附/聚集的能力，也不干扰ACh或L-Arg抑制黏附/聚集的能力。我们得出结论，在小鼠脑微循环中，L-NMMA和NNA收缩小动脉的能力、L-NMMA抑制ACh或L-Arg引起的扩张的能力以及L-NMMA增强血小板黏附/聚集的能力均与干扰依赖于“经典”内皮源性舒张因子（EDRF ACh）的现象有关。然而，在本实验中，L-NMMA或NNA的作用可能不是由于竞争性抑制从L-Arg产生EDRF ACh的酶。相反，L-NMMA和NNA似乎激活环氧化酶，导致超氧化物生成，从而使EDRF ACh失活。
