Effect of volatile anesthetics on the ion-channels of the cerebral vascular smooth muscle isolated from dog

(1)犬无内皮脑动脉环在静息状态下维持自律性肌源性张力，而肠系膜动脉无此功能。在无钙林格液和硝苯地平存在时，肌源性张力被取消。这些发现提示，电压依赖性钙通道基础钙内流的增加是维持脑血管肌源性张力的机制之一。氟烷显著抑制脑动脉环的肌源性张力。(2)加入四乙基铵和查氏毒素(钙激活的K++通道抑制剂)，在大脑动脉产生浓度依赖的收缩，但在肠系膜动脉不产生。这些结果提示，脑动脉钙离子内流的增加使钙激活的钾通道高度激活。氟烷即使在0.5MAC的低浓度下也能强烈地减弱四乙基铵和河豚毒素引起的张力发展。(3)用苯肾上腺素预先收缩的肠系膜动脉环在氟烷(4MAC)中引起快速收缩，在5~10min内达到平台期。在稳定后，氟烷的终止产生了短暂而深刻的松弛。Na~+-K~+-ATPase抑制剂哇巴因以浓度依赖的方式抑制这种松弛。在Ringer溶液中，Li~(2+)取代Na~(2+)也减弱了弛豫。这些结果表明，停氟烷引起的松弛可能与肠系膜动脉Na~+-K~+-ATPaes活性改变有关。挥发性麻醉药对细胞内离子浓度(Na~(++)、Ca~(++)、~(++))的影响正在本实验室进行。

(1) The rings of the dog cerebral artery without endothelium but not the mesenteric artery maintained an automatic myogenic tone in the resting state. The myogenic tone was abolished in the Ca^<++> free Ringer solution and in the presence of nifedipine. These findings suggest that the increased basal Ca^<++> influx through voltage-dependent Ca^<++> channel is responsible for the maintenance of myogenic tone in the cerebral artery. Halothane significantly inhibited the myogenic tone observed in the cerebral arterial rings.(2) The addition of tetraethylammonium and charybdotoxin (Ca^<++>-activated K^+ channel inhibitors) produced a concentration-dependent contraction in the cerebral artery, but not in the mesenteric artery. These findings suggest that Ca^<++>-activated K^+ channel was highly activated by the increased Ca^<++> influx in the cerebral artery. Halothane, even at a low concentration of 0.5 MAC,strongly attenuated the tension development elicited by tetraethylammonium and charybdotoxin.(3) Exposure of the mesenteric arterial rings precontracted with phenylephrine to halothane (4 MAC) caused a rapid contraction, which reached a plateau within 5 to 10 min. After stabilization, termination of halothane produced a transient and profound relaxation. This relaxation was inhibited by ouabain, a Na^+-K^+ ATPase inhibitor, in a concentration-dependent manner. Substitution of Li^+ for Na^+ in Ringer solution also attenuated the relaxation. These results suggest that the relaxation elicited by termination of halothane exposure may be responsible to an alteration of Na^+-K^+ ATPaes activity in the mesenteric artery.The effect of volatile anesthetics on the alteration of intracellular ion concentration (Na^+, Ca^<++>) is now under way in our laboratory.