Effects of β1-adrenergic receptor blockade on the cerebral microcirculation in the normal state and during global brain ischemia/reperfusion injury in rabbits
Effects of β1-adrenergic receptor blockade on the cerebral microcirculation in the normal state and during global brain ischemia/reperfusion injury in rabbits
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DOI：
10.1186/s40360-020-0394-7
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发表时间：
2020-02-21
影响因子：
2.9
通讯作者：
Matsukawa, Takashi
中科院分区：
文献类型：
--
作者：
Asano, Nobumasa;Hishiyama, Sohei;Matsukawa, Takashi
背景虽然最近的研究使用缺血性脑损伤的实验模型表明，全身给予β 1受体阻滞剂对脑血管系统具有潜在的保护作用，但确切的机制仍不清楚。除了心血管作用外，水溶性β（1）受体阻滞剂还可以通过血脑屏障，并可能对脑微血管发挥血管作用。本研究的目的是利用颅窗法研究β 1受体阻滞剂对正常状态和缺血/再灌注状态脑微血管的直接影响。方法采用闭合颅窗法观察成年雄性家兔脑微循环及软脑膜微动脉直径的变化。在第一个实验中，将不同浓度的选择性β（1）受体阻滞剂兰地洛尔注入颅窗，以评估剂量反应。在第二个实验中，研究了在缺血/再灌注损伤期间β（1）-阻滞剂对脑的影响。通过夹闭头臂动脉、左颈总动脉和左锁骨下动脉15 min诱导全脑缺血/再灌注。在缺血开始后5 min至再灌注后120 min输注兰地洛尔或人工脑脊液。记录缺血前、缺血中、再灌注后5、10、20、40、60、80、100、120 min软膜小动脉直径、血流动力学和生理学参数。结果在第一个实验中，局部给予较高浓度的兰地洛尔可使软脑膜小动脉轻度扩张（10（- 8）mol/L：4.3 ± 3.4%，10（- 6）mol/L：8.0 ± 5.8%，10（- 4）mol/L：7.3 ± 4.0%）。在第二个实验中，局部施用兰地洛尔在缺血/再灌注损伤期间显著扩张软脑膜小动脉直径（缺血：30.6 +/-38.6%，5分钟：47.3 +/-42.2%，10分钟：47.8 +/-34.2%，20分钟：38.0 +/- 39.0%）。兰地洛尔组和对照组之间的血流动力学和生理参数无统计学差异。结论阻断β 1肾上腺素能受体可使软脑膜微动脉在缺血/再灌注损伤时明显舒张。相比之下，在正常状态下仅观察到微动脉的轻微扩张，表明缺血性脑微血管比正常微血管更容易受到选择性阻断β（1）-肾上腺素能受体诱导的血管扩张效应的影响。
Background Although recent studies using experimental models of ischemic brain injury indicate that systemically-administered beta(1)-blockers have potential protective effects on the cerebrovascular system, the precise mechanisms remain unclear. In addition to their cardiovascular effects, water-soluble beta(1)-blockers can pass the blood-brain barrier and may exert their vascular action on cerebral microvessels. The aim of this study was to investigate the direct effects of beta(1)-blockade on the cerebral microvasculature both in the normal state and ischemia/reperfusion state using the cranial window method. Methods The closed cranial window method was used to visualize the cerebral microcirculation and changes in the pial arteriole diameter in adult male rabbits. In the first experiment, various concentrations of the selective beta(1)-blocker landiolol were administered into the cranial window to evaluate the dose-response. In the second experiment, the effect of beta(1)-blockade on the brain during ischemic/reperfusion injury was investigated. Global brain ischemia/reperfusion was induced by clamping the brachiocephalic, left common carotid, and left subclavian arteries for 15 min. Either landiolol or artificial cerebrospinal fluid was infused 5 min after initiation of ischemia through 120 min after reperfusion. Pial arteriole diameter and hemodynamic and physiological parameters were recorded before ischemia, during ischemia, and 5, 10, 20, 40, 60, 80, 100, and 120 min after reperfusion. Results In the first experiment, topical administration of landiolol at higher concentrations produced slight pial arteriole dilation (10(- 8) mol/L: 4.3 +/- 3.4%, 10(- 6) mol/L: 8.0 +/- 5.8%, 10(- 4) mol/L: 7.3 +/- 4.0%). In the second experiment, the topical administration of landiolol significantly dilated the pial arteriole diameters during ischemia/reperfusion injury (ischemia: 30.6 +/- 38.6%, 5 min: 47.3 +/- 42.2%, 10 min: 47.8 +/- 34.2%, 20 min: 38.0 +/- 39.0%). There were no statistical differences in hemodynamic and physiological parameters between the landiolol and control groups. Conclusions The blockade of beta(1)-adrenergic receptors induced significant vasodilation of pial arterioles during ischemia/reperfusion injury. By contrast, only a slight dilation of the arterioles was observed in the normal state, indicating that ischemic cerebral microvessels are more susceptible to the vasodilatory effect induced by selective blockade of beta(1)-adrenergic receptors than normal microvessels.