Marrelli S P, Johnson T D, Khorovets A, Childres W F, Bryan R M
Department of Anesthesiology, Baylor College of Medicine, Houston, Tex 77030, USA.
Stroke. 1998 Jul;29(7):1469-74. doi: 10.1161/01.str.29.7.1469.
Several recent studies have demonstrated that inward rectifier potassium channels (K(ir)s) are located on vascular smooth muscle of cerebral arteries in the rat. Activation of the K(ir)s dilates the arteries by relaxing the vascular smooth muscle. We tested the following hypothesis in the present study: function of inward rectifier potassium channels is altered after ischemia/reperfusion (I/R).
Temporary (2-hour) focal ischemia was induced in male Long-Evans rats (3% isoflurane anesthesia) by the intraluminal filament model. After 24 hours of reperfusion, ipsilateral and contralateral middle cerebral arteries (MCAs) were harvested and mounted on micropipettes, pressurized to 85 mm Hg, and luminally perfused.
Resting diameters for contralateral (control) and ipsilateral (I/R) MCAs were not significantly different (215+/-4 microm and 211+/-5 microm [n = 6 and n = 7], respectively). Activation of the K(ir)s by abluminal administration of 15 mmol/L KCl to the control MCAs dilated the MCA by 34+/-4% (n = 8). Activation of the K(ir)s in I/R MCAs produced a dilation of only 11+/-3% (n = 8; P<0.001 compared with control). BaCl2 (75 micromol/L), a concentration-selective inhibitor of the K(ir)s, significantly attenuated the dilation produced by 15 mmol/L KCl in control MCAs but not in the I/R MCAs. Endothelial-mediated dilations elicited by the luminal administration of uridine triphosphate (10 micromol/L) produced similar dilations in both groups (32+/-5% for sham [n = 4] and 33+/-2% for I/R [n = 4]), indicating that dilator function in general was not altered in I/R vessels.
We conclude that Kir function is altered after I/R. The Kir altered function is likely to exacerbate the brain injury occurring after I/R.
最近的几项研究表明，内向整流钾通道（K(ir)s）位于大鼠脑动脉的血管平滑肌上。激活K(ir)s可通过舒张血管平滑肌使动脉扩张。在本研究中，我们检验了以下假设：缺血/再灌注（I/R）后内向整流钾通道的功能会发生改变。
采用管腔内插入线栓模型，对雄性Long-Evans大鼠（3%异氟烷麻醉）诱导暂时性（2小时）局灶性缺血。再灌注24小时后，获取同侧和对侧大脑中动脉（MCA），安装在微量移液器上，加压至85 mmHg，并进行腔内灌注。
对侧（对照）和同侧（I/R）MCA的静息直径无显著差异（分别为215±4μm和211±5μm [n = 6和n = 7]）。向对照MCA的腔外给予15 mmol/L KCl激活K(ir)s可使MCA扩张34±4%（n = 8）。激活I/R MCA中的K(ir)s仅产生11±3%的扩张（n = 8；与对照相比，P<0.001）。BaCl2（75 μmol/L）是K(ir)s的浓度选择性抑制剂，可显著减弱15 mmol/L KCl在对照MCA中产生的扩张，但对I/R MCA无效。腔内给予三磷酸尿苷（10 μmol/L）引起的内皮介导的扩张在两组中相似（假手术组为32±5% [n = 4]，I/R组为33±2% [n = 4]），表明I/R血管中的扩张功能总体上未改变。
我们得出结论，I/R后Kir功能发生改变。Kir功能改变可能会加重I/R后发生的脑损伤。
