Tsuji T, Cook D A
Department of Neurosurgery, Shinshu University, Matsumoto, Japan.
J Cardiovasc Pharmacol. 1992;20 Suppl 12:S109-13. doi: 10.1097/00005344-199204002-00031.
The responses to intraluminally applied substance P (SP) were examined in isolated and perfused canine basilar arteries using the stainless-steel cannula inserting method. In control vessels with intact endothelium, this peptide induced a monophasic dilation at lower doses, and a biphasic response, i.e., an initial dilation followed by a secondary constriction at higher doses. After extraluminal treatment with oxyhemoglobin, the dilation was attenuated and the constriction was augmented. After endothelial removal with intraluminal saponin, the dilation was reduced and the constriction was enhanced significantly. This potentiated constriction was significantly depressed by indomethacin (a cyclooxygenase inhibitor), OKY-046 (a thromboxane synthetase inhibitor), and nimodipine (a calcium antagonist), but not by AA-861 (a lipoxygenase inhibitor). These results suggest that SP has two distinct effects (an endothelium-dependent dilation and a direct constriction) and that the potentiated constriction in the absence of endothelium may be related to the action of thromboxane A2, linked with calcium influx into the smooth muscle cells of cerebral arteries. This mechanism may be implicated in cerebral vasospasm after subarachnoid hemorrhage.
采用不锈钢套管插入法，在分离并灌注的犬基底动脉中检测了腔内应用P物质（SP）后的反应。在具有完整内皮的对照血管中，该肽在较低剂量时诱导单相舒张，在较高剂量时诱导双相反应，即初始舒张后继发收缩。用氧合血红蛋白进行腔外处理后，舒张减弱而收缩增强。用腔内皂苷去除内皮后，舒张降低且收缩显著增强。吲哚美辛（一种环氧化酶抑制剂）、OKY - 046（一种血栓素合成酶抑制剂）和尼莫地平（一种钙拮抗剂）可显著抑制这种增强的收缩，但脂氧合酶抑制剂AA - 861则无此作用。这些结果表明，SP具有两种不同的作用（内皮依赖性舒张和直接收缩），并且在无内皮情况下增强的收缩可能与血栓素A2的作用有关，血栓素A2与钙流入脑动脉平滑肌细胞有关。该机制可能与蛛网膜下腔出血后的脑血管痉挛有关。
