尼可地尔对猫脊髓缺血后反射电位恢复的影响。

Effects of nicorandil on the recovery of reflex potentials after spinal cord ischaemia in cats.

作者信息

Suzuki T, Sekikawa T, Nemoto T, Moriya H, Nakaya H

机构信息

Department of Pharmacology, School of Medicine, Chiba University, Japan.

出版信息

Br J Pharmacol. 1995 Sep;116(2):1815-20. doi: 10.1111/j.1476-5381.1995.tb16668.x.

DOI:10.1111/j.1476-5381.1995.tb16668.x

PMID:8528565

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1909092/

Abstract

The pathophysiological significance of ATP-sensitive K+ (KATP) channels in the central nervous system is not fully understood. In this study the effects of nicorandil (a hybrid vasodilator having a dual mechanism of action as a K+ channel opener and a nitrate) on the recovery of the spinal cord reflex potentials after spinal cord ischaemia were examined and compared with those of pinacidil and nitroprusside in anaesthetized spinal cats. 2. Spinal cord ischaemia was produced by occlusion of the thoracic aorta and the bilateral internal mammary arteries for 10 min. Regional blood flow in the spinal cord was continuously measured with a laser-Doppler flow meter. The monosynaptic (MSR) and polysynaptic reflex (PSR) potentials, elicited by electrical stimulation of the tibial nerve, were recorded from the lumbo-sacral ventral root. The recovery process of spinal reflex potentials was reproducible when the occlusion was repeated twice at an interval of 120 min. 3. Pretreatment with nicorandil (30-100 micrograms kg-1) accelerated the recovery of PSR potentials after spinal cord ischaemia. Such an accelerating effect on the recovery of PSR potentials was also shared by pinacidil (100 micrograms kg-1), another K+ channel opener. In addition, the accelerating effect of nicorandil (100 micrograms kg-1) on the recovery of PSR potentials was abolished by co-administration of glibenclamide (3 mg kg-1), a sulphonylurea KATP channel blocker. Nitroprusside (8 micrograms kg-1min-1) retarded rather than improved the recovery of PSR potentials after spinal cord ischaemia. All of these drugs failed to improve the spinal cord blood flow during ischaemia and reperfusion. 4 These results suggest that nicorandil promotes the recovery of polysynaptic reflex potentials after spinal cord ischaemia by opening the KATP channels of neurones rather than by increasing local bloodflow. K+ channel openers may exert a salutary effect on the functional recovery of the ischaemic spinal cord.

摘要

三磷酸腺苷敏感性钾（KATP）通道在中枢神经系统中的病理生理意义尚未完全明确。在本研究中，我们检测了尼可地尔（一种具有钾通道开放剂和硝酸盐双重作用机制的混合型血管扩张剂）对脊髓缺血后脊髓反射电位恢复的影响，并在麻醉的脊髓猫中将其与匹那地尔和硝普钠的作用进行了比较。2. 通过阻断胸主动脉和双侧乳内动脉10分钟来造成脊髓缺血。用激光多普勒流量计连续测量脊髓局部血流量。由胫神经电刺激诱发的单突触（MSR）和多突触反射（PSR）电位，从腰骶部腹根记录。当以120分钟的间隔重复阻断两次时，脊髓反射电位的恢复过程具有可重复性。3. 尼可地尔（30 - 100微克/千克）预处理可加速脊髓缺血后PSR电位的恢复。另一种钾通道开放剂匹那地尔（100微克/千克）对PSR电位的恢复也有这种加速作用。此外，格列本脲（3毫克/千克），一种磺酰脲类KATP通道阻滞剂，共同给药可消除尼可地尔（100微克/千克）对PSR电位恢复的加速作用。硝普钠（8微克/千克·分钟）在脊髓缺血后延迟而非改善了PSR电位的恢复。所有这些药物在缺血和再灌注期间均未能改善脊髓血流量。4. 这些结果表明，尼可地尔通过开放神经元的KATP通道而非增加局部血流量来促进脊髓缺血后多突触反射电位的恢复。钾通道开放剂可能对缺血脊髓的功能恢复产生有益作用。