Cyclooxygenase-1 participates in selected vasodilator responses of the cerebral circulation
Cyclooxygenase-1 participates in selected vasodilator responses of the cerebral circulation
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DOI：
10.1161/01.res.88.6.600
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发表时间：
2001-03-30
影响因子：
20.1
通讯作者：
Iadecola, C
中科院分区：
文献类型：
--
作者：
Niwa, K;Haensel, C;Iadecola, C
环氧合酶（COX）是一种前列腺素合成酶，存在于COX-1和COX-2两种亚型中。尽管长期以来人们一直假设前列腺素参与脑血管调节，但由于缺乏足够的药理学工具，导致结果相互矛盾，并且研究人员无法确定COX-1和COX-2的相对作用。我们使用COX-1抑制剂SC-560和COX-1 null （COX-1(-/-)）小鼠来研究COX-1是否在脑血管调节中发挥作用。小鼠被麻醉（氨基甲酸乙酯和氯氯蔗糖），并配备一个颅窗。采用激光多普勒血流仪或c -14-碘安替比林定量放射自显影技术测量脑血流（CBF）。在野生型小鼠中，SC-560 （25 μ mol/L）使静息CBF减少21% +/-4%，并减弱局部应用缓激肽（-59%）或钙离子离子A23187（-49%）和全身高碳血症（-58%）产生的CBF增加(P
Cyclooxygenase (COX) is a prostanoid-synthesizing enzyme present in 2 isoforms: COX-1 and COX-2. Although it has long been hypothesized that prostanoids participate in cerebrovascular regulation, the lack of adequate pharmacological tools has led to conflicting results and has not permitted investigators to define the relative contribution of COX-1 and COX-2. We used the COX-1 inhibitor SC-560 and COX-1-null (COX-1(-/-)) mice to investigate whether COX-1 plays a role in cerebrovascular regulation. Mice were anesthetized (urethane and chloralose) and equipped with a cranial window. Cerebral blood flow (CBF) was measured by laser Doppler flowmetry or by the C-14-iodoantipyrine technique with quantitative autoradiography. In wild-type mice, SC-560 (25 mu mol/L) reduced resting CBF by 21+/-4% and attenuated the CBF increase produced by topical application of bradykinin (-59%) or calcium ionophore A23187 (-49%) and by systemic hypercapnia (-58%) (P