Högestätt E D, Uski T K
Gen Pharmacol. 1987;18(2):111-7. doi: 10.1016/0306-3623(87)90235-7.
The effects of some prostaglandins (PG's) and leukotrienes (LT's) on rat middle cerebral, basilar and mesenteric arteries were evaluated in vitro. The order of potency of some prostanoids with respect to their contractile effects in basilar arteries was: U44069 greater than PGF2 alpha greater than PGI2 approximately equal to PGE2 greater than 6-keto-PGE1 greater than 6-keto-PGF1 alpha, whereas 6,15-diketo-PGF1 alpha was inactive. Middle cerebral and basilar arteries were 3-5 times more sensitive than mesenteric arteries to PGF2 alpha. LTD4 and LTC4 were inactive in all three vessel types. PGI2 produced a concentration-related relaxation of similar potency in all three arteries contracted by PGF2 alpha. Arteries preactivated by other agents (K+, noradrenaline, 5-hydroxytryptamine) either failed to relax or inconsistently relaxed after PGI2 application. Among the PGI2 metabolites (6-keto-PGF1 alpha, 6,15-diketo-PGF1 alpha, 6-keto-PGE1), only 6-keto-PGE1 elicited relaxation in the PGF2 alpha-contracted basilar artery. However, the drug potency was significantly smaller than that of PGI2. Nifedipine inhibited the PGF2 alpha-induced contraction by 68% in middle cerebral arteries and by 80% in mesenteric arteries. Exposure to Ca2+-free medium for a time period which almost completely abolished the contractile response to K+ (less than 5% left), reduced the PGF2 alpha-induced contraction by 54, 61 and 85% in middle cerebral, basilar and mesenteric arteries, respectively. The PGF2 alpha-induced contraction of cerebral arteries in Ca2+-free medium was usually composed of a rapidly developing first phase, which levelled off after 1-2 min, and a second slowly developing tonic phase.(ABSTRACT TRUNCATED AT 250 WORDS)
体外评估了一些前列腺素（PG）和白三烯（LT）对大鼠大脑中动脉、基底动脉和肠系膜动脉的影响。一些前列腺素在基底动脉中的收缩效力顺序为：U44069＞前列腺素F2α＞前列环素（PGI2）≈前列腺素E2＞6-酮-前列腺素E1＞6-酮-前列腺素F1α，而6,15-二酮-前列腺素F1α无活性。大脑中动脉和基底动脉对前列腺素F2α的敏感性比肠系膜动脉高3至5倍。白三烯D4（LTD4）和白三烯C4（LTC4）在所有三种血管类型中均无活性。PGI2使所有由前列腺素F2α收缩的三种动脉产生浓度相关的类似效力的舒张作用。用其他药物（钾离子、去甲肾上腺素、5-羟色胺）预激活的动脉在应用PGI2后要么不舒张，要么舒张不一致。在PGI2代谢产物（6-酮-前列腺素F1α、6,15-二酮-前列腺素F1α、6-酮-前列腺素E1）中，只有6-酮-前列腺素E1在前列腺素F2α收缩的基底动脉中引起舒张。然而，该药效力明显小于PGI2。硝苯地平在大脑中动脉中抑制前列腺素F2α诱导的收缩68%，在肠系膜动脉中抑制80%。暴露于无钙培养基一段时间，几乎完全消除对钾离子的收缩反应（剩余不到5%），分别使大脑中动脉、基底动脉和肠系膜动脉中前列腺素F2α诱导的收缩减少54%、61%和85%。在无钙培养基中，前列腺素F2α诱导的脑动脉收缩通常由快速发展的第一相组成，1至2分钟后趋于平稳，以及第二相缓慢发展的强直相。（摘要截短于250字）
