Schilling L, Parsons A A, Wahl M
Department of Physiology, University of Munich, Germany.
J Neurosurg. 1995 Jul;83(1):123-8. doi: 10.3171/jns.1995.83.1.0123.
The smooth-muscle relaxant action of adenosine 5'-triphosphate (ATP)-sensitive potassium (KATP) channels in cerebral arteries of large diameter has been confirmed in a number of in vitro studies, but there is still debate about the presence of KATP channels in small cerebral arteries. In the present study, the authors compare the effects of cromakalim and bimakalim, two putative KATP channel activators, in different parts of the feline isolated middle cerebral artery (MCA) designated proximal, intermediate, and distal. The latter corresponds to those small pial arteries that are usually studied in vivo. In ring segments precontracted with 10(-5) M of uridine-5-triphosphate (UTP), both cromakalim and bimakalim induced concentration-related relaxation, with bimakalim being more potent than cromakalim, and no significant differences noted among segments obtained from the different regions of the MCA. In vessels precontracted by adding 30 mM KCl the potency of cromakalim and bimakalim was reduced compared with that obtained after UTP precontraction. In the presence of 10(-6) M glibenclamide, an antagonist of KATP channel activators, the concentration-effect curve to bimakalim was shifted to the right in the proximal and distal MCA, indicating a similar route of action for bimakalim and cromakalim in these arteries. The present study therefore indicates the presence of KATP channels in isolated small cerebral arteries according to results obtained in vivo. Activators of KATP channesl may prove helpful in the treatment of vasospasm, which may occur in large and small cerebral arteries after subarachnoid hemorrhage.
大直径脑动脉中三磷酸腺苷(ATP)敏感性钾(KATP)通道的平滑肌舒张作用已在多项体外研究中得到证实,但关于小脑动脉中是否存在KATP通道仍存在争议。在本研究中,作者比较了两种假定的KATP通道激活剂——克罗卡林和比马卡林,对猫离体大脑中动脉(MCA)不同部位(近端、中间和远端)的影响。后者对应于通常在体内研究的小软脑膜动脉。在用10⁻⁵M尿苷-5-三磷酸(UTP)预收缩的环段中,克罗卡林和比马卡林均诱导出浓度相关的舒张,比马卡林比克罗卡林更有效,且从MCA不同区域获得的节段之间未观察到显著差异。在通过添加30 mM氯化钾预收缩的血管中,克罗卡林和比马卡林的效力与UTP预收缩后相比有所降低。在存在10⁻⁶M格列本脲(一种KATP通道激活剂拮抗剂)的情况下,比马卡林在近端和远端MCA的浓度-效应曲线向右移动,表明比马卡林和克罗卡林在这些动脉中的作用途径相似。因此,根据体内获得的结果,本研究表明在离体小脑动脉中存在KATP通道。KATP通道激活剂可能被证明有助于治疗蛛网膜下腔出血后大小脑动脉可能发生的血管痉挛。