Schulz R, Krueger C, Manickavel V, Steele J A, Cook D A
Department of Pediatrics, University of Alberta, Edmonton, Canada.
Pharmacology. 1993 Apr;46(4):211-23. doi: 10.1159/000139048.
Hydroperoxyeicosatetraenoic acids (HPETEs) are potent vasoconstrictors which have been implicated in the pathogenesis of the delayed cerebrovascular spasm which follows subarachnoid haemorrhage. We have previously shown that one of their stable breakdown products, 15-hydroxyeicosatetraenoic acid (15-HETE), is the major lipoxygenase product released from isolated cerebral arteries. To investigate the vascular cell type responsible for their production we have established the culture of smooth muscle cells from cerebral arteries and have measured their release of HETEs upon stimulation with arachidonic acid. The cultured cells isolated from bovine cerebral arteries expressed smooth muscle phenotype as they stained positively for smooth muscle alpha-actin and not factor VIII-related antigen. Furthermore, these cells possessed the calcium and potassium conductances characteristic of smooth muscle cells. Upon incubation with arachidonic acid, the major lipoxygenase product was 15-HETE; no leukotrienes were detected. The formation of 15-HETE was concentration-dependent and was attenuated by nordihydroguaiaretic acid, but not by indomethacin. Similar to intact cerebral artery, cultured cerebrovascular smooth muscle cells have lipoxygenase activity, the major product of which is 15-HETE. These results are consistent with a possible role of the HPETEs in the pathogenesis of cerebral vasospasm.
氢过氧化二十碳四烯酸（HPETEs）是强效血管收缩剂，与蛛网膜下腔出血后迟发性脑血管痉挛的发病机制有关。我们之前已经表明，它们的一种稳定分解产物，15-羟基二十碳四烯酸（15-HETE），是从离体脑动脉释放的主要脂氧合酶产物。为了研究负责其产生的血管细胞类型，我们建立了脑动脉平滑肌细胞培养体系，并测量了它们在花生四烯酸刺激下HETEs的释放量。从牛脑动脉分离的培养细胞表现出平滑肌表型，因为它们对平滑肌α-肌动蛋白染色呈阳性，而对VIII因子相关抗原染色呈阴性。此外，这些细胞具有平滑肌细胞特有的钙和钾电导。与花生四烯酸一起孵育时，主要的脂氧合酶产物是15-HETE；未检测到白三烯。15-HETE的形成呈浓度依赖性，并被去甲二氢愈创木酸减弱，但不受吲哚美辛影响。与完整脑动脉相似，培养的脑血管平滑肌细胞具有脂氧合酶活性，其主要产物是15-HETE。这些结果与HPETEs在脑血管痉挛发病机制中可能发挥的作用一致。
