Copeland J R, Willoughby K A, Tynan T M, Moore S F, Ellis E F
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0613.
Am J Physiol. 1995 Jan;268(1 Pt 2):H458-66. doi: 10.1152/ajpheart.1995.268.1.H458.
Aspirin (acetylsalicylic acid, ASA) was administered to rabbits in an attempt to inhibit selectively endothelial cyclooxygenase activity and therefore to determine its role in bradykinin-induced radical-mediated dilation of cerebral arterioles. With the use of the cranial window technique in anesthetized rabbits, pial arteriolar diameters were recorded in response to topically applied bradykinin, acetylcholine, and ventilation with 10% O2-9% CO2 gas mixture. Prostaglandins were measured in isolated cerebral microvessels and cerebrospinal fluid (CSF) using radioimmunoassay. Microvessel prostaglandin production was reduced significantly by 90 mg/kg i.v. ASA, whereas acetylcholine-stimulated increases of CSF prostaglandins were not similarly affected. This treatment reduced bradykinin-induced dilation of pial arterioles by 47%. After concurrent 90 mg/kg i.v. ASA plus 300 microM ASA topically applied to the brain, stimulated increases of CSF prostaglandins were reduced by 79%, while bradykinin-induced dilation was reduced by 78%. ASA did not reduce the dilator activity of either acetylcholine or ventilation with 10% O2-9% CO2. Acetylcholine- but not bradykinin-induced dilation was reduced by NG-nitro-L-arginine methyl ester. These results indicate intravenous ASA produced a relatively selective inhibition of cerebral microvascular cyclooxygenase and partial inhibition of bradykinin-induced dilation. Further inhibition of dilation occurred following ASA administered both systemically and topically to the brain. This indicates two sources of cyclooxygenase, endothelial and nonendothelial, mediate the bradykinin-induced dilation of rabbit pial arterioles. Furthermore, systemic doses of ASA do not eliminate brain prostaglandin formation.
给兔子服用阿司匹林（乙酰水杨酸，ASA），试图选择性抑制内皮细胞环氧化酶活性，从而确定其在缓激肽诱导的脑小动脉自由基介导的扩张中的作用。在麻醉的兔子中使用颅窗技术，记录软脑膜小动脉直径对局部应用缓激肽、乙酰胆碱以及用10% O₂ - 9% CO₂气体混合物通气的反应。使用放射免疫分析法测定分离的脑微血管和脑脊液（CSF）中的前列腺素。静脉注射90 mg/kg ASA可使微血管前列腺素生成显著降低90%，而乙酰胆碱刺激引起的CSF前列腺素增加未受到类似影响。这种处理使缓激肽诱导的软脑膜小动脉扩张减少了47%。在静脉注射90 mg/kg ASA并同时在脑局部应用300 μM ASA后，刺激引起的CSF前列腺素增加减少了79%，而缓激肽诱导的扩张减少了78%。ASA并未降低乙酰胆碱或10% O₂ - 9% CO₂通气的扩张活性。NG - 硝基 - L - 精氨酸甲酯可降低乙酰胆碱而非缓激肽诱导的扩张。这些结果表明静脉注射ASA对脑微血管环氧化酶产生了相对选择性抑制，并部分抑制了缓激肽诱导的扩张。在对脑进行全身和局部应用ASA后，扩张进一步受到抑制。这表明环氧化酶的两个来源，即内皮细胞和非内皮细胞，介导了缓激肽诱导的兔软脑膜小动脉扩张。此外，全身剂量的ASA并未消除脑内前列腺素的形成。
