Kanamaru K, Weir B K, Findlay J M, Krueger C A, Cook D A
Division of Neurosurgery, University of Alberta, Edmonton, Canada.
J Neurosurg. 1989 Dec;71(6):909-15. doi: 10.3171/jns.1989.71.6.0909.
Chronic cerebral vasospasm was induced in 16 monkeys by direct placement of a clot of autologous blood over the arteries of the circle of Willis on the right side. The middle cerebral arteries (MCA's) on the clot side all showed angiographic vasospasm, which was maximal 7 days after subarachnoid hemorrhage. Animals were sacrificed at this time and vascular responses to acetylcholine (ACh), histamine, and the calcium ionophore A23187 were studied in MCA rings from the clot (spastic) side and the non-clot (control) side. In control preparations with an intact endothelium, which had been precontracted by prostaglandin F2 alpha (PGF2 alpha), histamine and A23187 produced significant relaxation. The same concentrations of histamine and A23187 did not relax vascular tissues in which the endothelium had been mechanically removed. Acetylcholine did not produce a significant endothelium-dependent relaxation of primate MCA rings, but did relax rings of primate common carotid artery. Pretreatment with chlorpheniramine (an H1-receptor antagonist) prevented histamine-induced relaxation; however, cimetidine (an H2-receptor antagonist) had no inhibitory action. It thus seems that histamine mediates relaxation of intact MCA's mostly by an H1-receptor-mediated release of endothelium-derived relaxing factor (EDRF). Relaxations induced by histamine and A23187 in MCA's from the clot side were substantially reduced. Moreover, the small component of ACh-induced relaxation was also abolished. Endothelium-independent relaxation induced by glyceryl trinitrate (GTN) occurred in arteries from both the control and the clot sides. Constrictions induced by KC1 and PGF2 alpha were reduced on the clot side of the MCA's. These results suggest that subarachnoid hemorrhage influences both the generation of EDRF and the constriction of affected arteries. The small contraction which was elicited in spastic arteries was fully relaxed by GTN.
通过在16只猴子右侧 Willis 环动脉上直接放置自体血凝块诱导慢性脑血管痉挛。血凝块侧的大脑中动脉（MCA）均显示血管造影血管痉挛，蛛网膜下腔出血后7天最为严重。此时处死动物，研究血凝块（痉挛）侧和非血凝块（对照）侧 MCA 环对乙酰胆碱（ACh）、组胺和钙离子载体 A23187 的血管反应。在具有完整内皮的对照制剂中，前列腺素 F2α（PGF2α）预收缩后，组胺和 A23187 产生显著舒张。相同浓度的组胺和 A23187 不能使内皮已被机械去除的血管组织舒张。乙酰胆碱不能使灵长类动物 MCA 环产生显著的内皮依赖性舒张，但能使灵长类动物颈总动脉环舒张。用氯苯那敏（一种 H1 受体拮抗剂）预处理可防止组胺诱导的舒张；然而，西咪替丁（一种 H2 受体拮抗剂）没有抑制作用。因此，组胺似乎主要通过 H1 受体介导的内皮源性舒张因子（EDRF）释放来介导完整 MCA 的舒张。血凝块侧 MCA 中组胺和 A23187 诱导的舒张明显减少。此外，ACh 诱导的小部分舒张也被消除。硝酸甘油（GTN）诱导的非内皮依赖性舒张在对照侧和血凝块侧的动脉中均发生。MCA 血凝块侧 KC1 和 PGF2α 诱导的收缩减少。这些结果表明蛛网膜下腔出血影响 EDRF 的产生和受影响动脉的收缩。GTN 可使痉挛动脉中引发的小收缩完全舒张。
