Effects of topical and intravenous JM-1232(-) infusion on cerebrovascular reactivity in rats
Effects of topical and intravenous JM-1232(-) infusion on cerebrovascular reactivity in rats
复制标题
局部和静脉输注JM-1232(-)对大鼠脑血管反应性的影响
DOI：
10.1007/s00540-015-2017-9
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发表时间：
2015
期刊：
影响因子：
2.8
通讯作者：
Tanabe K
中科院分区：
文献类型：
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作者：
Iwata K;Iida H;Iida M;Fukuoka N;Kito K;Tanabe K
一种新型的短效苯二氮卓受体激动剂JM-1232（−）已被证明具有镇静/催眠作用和广泛的安全边际。然而，它对脑血管的影响尚不清楚。因此，我们研究了局部和静脉注射JM-1232（−）以及低血压或高碳酸血症时静脉注射JM-1232（−）的脑血管反应性。在异氟醚麻醉大鼠后，我们采用封闭颅窗制备方法测量脑动脉直径的变化。我们首先测量了外用JM-1232（−）的直接效应。然后我们确定静脉注射JM-1232（−）的效果，然后我们测量了JM-1232（-）输注前后对高碳酸血症的反应。最后，我们测量了JM-1232（−）输注前后对逐步诱导低血压的反应。局部输注JM-1232（−）扩张的动脉小动脉。静脉输注JM-1232（−）分别以0.1、0.3和1.0 mg/kg/min的剂量改变了4.5±2.7%、5.0±3.9%和−2.8±2.6%的动脉小动脉。在注射JM-1232（−）前后，高碳酸血症使头小动脉扩张。静脉注射JM-1232（−）前后低血压期间，心肌小动脉直径没有变化。这些结果表明，局部注射JM-1232（−）对心肌小动脉有扩张作用，静脉注射JM-1232（−）可能不会影响脑血管对低血压或高碳酸血症的反应性。
A novel short-acting benzodiazepine receptor agonist, JM-1232(−), has been shown to have a sedative/hypnotic effect and wide safety margin. However, its effect on cerebral vessels is not well known. Therefore, we investigated the cerebrovascular reactivity to topical and intravenous JM-1232(−) and during hypotension or hypercapnia with intravenous administration of JM-1232(−). We used a closed cranial window preparation to measure the changes of cerebral pial arteriolar diameters in isoflurane-anesthetized Sprague–Dawley rats. We first measured the direct effect of topical JM-1232(−). We then determined the effect of intravenous JM-1232(−) and then we measured the response to hypercapnia before and after JM-1232(–) infusion. Finally, we measured the reaction to stepwise induction of hypotension before and after JM-1232(−) infusion. Topical infusion of JM-1232(−) dilated pial arterioles. Intravenous infusion of JM-1232(−) changed pial arterioles by 4.5 ± 2.7 %, 5.0 ± 3.9 %, and −2.8 ± 2.6 % (at 0.1, 0.3, and 1.0 mg/kg/min, respectively). Hypercapnia dilated pial arterioles before and after JM-1232(−) infusion. The diameters of pial arterioles did not change during hypotension before or after intravenous JM-1232(−) infusion. These results indicate that topical JM-1232(−) has a dilative effect on pial arterioles and that intravenous administration of JM-1232(−) may not affect cerebrovascular reactivity to hypotension or hypercapnia.