There is considerable controversy regarding the vasoactive action of prostaglandin E2 (PGE2). On the one hand, indirect evidence implicates that astrocytic release of PGE2 contributes to neurovascular coupling responses mediating functional hyperemia in the brain. On the other hand, overproduction of PGE2 was also reported to contribute to cerebral vasospasm associated with subarachnoid hemorrhage. The present study was conducted to resolve this controversy by determining the direct vasoactive effects of PGE2 in resistance-sized human cerebral parenchymal arterioles. To achieve this goal PGE2-induced isotonic vasomotor responses were assessed in parenchymal arterioles isolated from fronto-temporo-parietal cortical tissues surgically removed from patients and expression of PGE2 receptors were examined. In functionally intact parenchymal arterioles lower concentrations of PGE2 (from 10-8 to 10-6 mol/l) caused significant, endothelium-independent vasorelaxation, which was inhibited by the EP4 receptor blocker BGC201531. In contrast, higher concentrations of PGE2 evoked significant EP1-dependent vasoconstriction, which could not be reversed by the EP4 receptor agonist CAY10598. We also confirmed previous observations that PGE2 primarily evokes constriction in intracerebral arterioles isolated from R. norvegicus. Importantly, vascular mRNA and protein expression of vasodilator EP4 receptors was significantly higher than that of vasoconstrictor EP1 receptors in human cerebral arterioles. PGE2 at low concentrations dilates whereas at higher concentrations constricts human cerebral parenchymal arterioles. This bimodal vasomotor response is consistent with both the proposed vasodilator role of PGE2 during functional hyperemia and its putative role in cerebral vasospasm associated with subarachnoid hemorrhage in human patients.

中文翻译：

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前列腺素E2是假定的神经血管偶联介质，低浓度时会扩张，而高浓度时会收缩人脑实质小动脉。

关于前列腺素E2（PGE2）的血管活性作用存在相当大的争议。一方面，间接证据暗示PGE2的星形细胞释放有助于介导大脑功能性充血的神经血管偶联反应。另一方面，PGE 2的过度产生也据报道与蛛网膜下腔出血相关的脑血管痉挛。本研究旨在通过确定PGE2在抵抗性大小的人脑实质小动脉中的直接血管活性作用来解决这一争议。为了实现该目标，在从患者手术切除的额颞叶顶皮质组织中分离的实质小动脉中评估了PGE 2诱导的等渗血管舒缩反应，并检查了PGE 2受体的表达。在功能完整的实质小动脉中，较低的PGE2浓度（从10-8至10-6 mol / l）引起明显的内皮依赖性血管舒张，这被EP4受体阻滞剂BGC201531抑制。相反，较高浓度的PGE2引起明显的EP1依赖性血管收缩，而EP4受体激动剂CAY10598不能逆转。我们还证实了以前的观察结果，即PGE2主要引起从R. norvegicus分离的脑小动脉收缩。重要的是，人脑小动脉中血管舒张剂EP4受体的血管mRNA和蛋白表达显着高于血管收缩剂EP1受体。低浓度的PGE2会扩张，而高浓度的PGE2会收缩人脑实质小动脉。