Tsuji T, Cook D A
Department of Neurosurgery, Shinshu University, Matsumoto, Japan.
J Cardiovasc Pharmacol. 1995 Jun;25(6):940-6. doi: 10.1097/00005344-199506000-00012.
We examined the responses to intraluminally applied acetylcholine (ACh) in isolated and perfused canine basilar arteries by the stainless-steel cannula-inserting method. In control vessels with intact endothelium, ACh produced a slight vasodilatation followed by a long-lasting vasoconstriction in the absence of induced tone. Propranolol, a beta-adrenoceptor blocker, had no effect on the response to ACh. After endothelial removal with intraluminal saponin, the constrictor component of the response to ACh was significantly enhanced, and the constrictions to prostaglandin F2 alpha (PGF2 alpha) and potassium chloride (KCl) were significantly potentiated. After exposure to extraluminal oxyhemoglobin, the ACh-induced constriction was significantly augmented, whereas the dilator component of the response to calcium ionophore A23187 was significantly attenuated. The enhanced constriction to ACh after endothelial removal was significantly blocked by OKY-046 (a thromboxane synthetase inhibitor) and nimodipine (a dihydropyridine calcium antagonist), but was slightly though not significantly suppressed by AA-861 (a lipoxygenase inhibitor). The response to PGF2 alpha was not altered by OKY-046 or AA-861. These results suggest that the potentiation of ACh-induced constriction after endothelial removal may be mediated in part by thromboxane A2 (TXA2), linked with extracellular calcium entry in smooth muscle cells (SMC). This mechanism might be involved in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH).
我们采用不锈钢套管插入法，研究了在体外用乙酰胆碱（ACh）灌注的离体犬基底动脉的反应。在具有完整内皮的对照血管中，在没有诱导张力的情况下，ACh引起轻微的血管舒张，随后是持久的血管收缩。β-肾上腺素能受体阻滞剂普萘洛尔对ACh的反应没有影响。用管腔内皂苷去除内皮后，对ACh反应的收缩成分显著增强，对前列腺素F2α（PGF2α）和氯化钾（KCl）的收缩作用显著增强。暴露于管腔外的氧合血红蛋白后，ACh诱导的收缩显著增强，而对钙离子载体A23187反应的舒张成分显著减弱。去除内皮后对ACh增强的收缩被OKY-046（一种血栓素合成酶抑制剂）和尼莫地平（一种二氢吡啶类钙拮抗剂）显著阻断，但被AA-861（一种脂氧合酶抑制剂）轻微但不显著地抑制。OKY-046或AA-861对PGF2α的反应没有改变。这些结果表明，去除内皮后ACh诱导的收缩增强可能部分由血栓素A2（TXA2）介导，与平滑肌细胞（SMC）中细胞外钙内流有关。这种机制可能参与蛛网膜下腔出血（SAH）后脑血管痉挛的发病机制。
