钾通道开放剂尼可地尔和钾通道阻断剂氯化铯对缺氧引起离体大鼠肺动脉收缩反应的影响  

Effects of CsCl and nicorandil on hypoxia induced contractile response of isolated rat pulmonary arteries

作　　者：王唯[1] 王逸平[1] 孙伟康 

机构地区：[1]中国科学院上海药物研究所,上海200031

出　　处：《中国药理学通报》1999年第6期547-550,共4页Chinese Pharmacological Bulletin

摘　　要：目的　观察钾通道开放剂尼可地尔和钾通道阻断剂氯化铯对缺氧引起离体大鼠肺动脉环收缩反应的影响。方法　以０．９５Ｎ２＋０．０５ＣＯ２造成肺动脉环的缺氧性收缩反应；机械法去除肺动脉血管内皮细胞。结果　急性缺氧１ｈ后，含内皮与去内皮肺动脉环的ＫＣｌ诱导的最大收缩百分率（ＴＫｍａｘ％）分别为１６％±４％、１８％±５％（Ｐ＞０．０５）。有氧时，钾通道阻滞剂氯化铯（１０、２０ｍｍｏｌ·Ｌ－１）可略微提高肺动脉环的收缩张力，氯化铯４０ｍｍｏｌ·Ｌ－１引起的明显收缩，依赖细胞外Ｃａ２＋内流。缺氧可增强氯化铯的上述作用，氯化铯（１０、２０、４０ｍｍｏｌ·Ｌ－１）诱导肺动脉环产生的ＴＫｍａｘ％分别增加７５０％、３５４％、１７％。钾通道开放剂尼可地尔（３、１０、３０μｍｏｌ·Ｌ－１）可浓度依赖性地抑制缺氧及氯化铯诱导的肺动脉环收缩反应。含内皮与去内皮肺动脉环在上述反应中有相似性的表现。结论　急性缺氧造成非内皮依赖性肺动脉收缩反应，与平滑肌钾通道阻滞有关。氯化铯可增强此反应。尼可地尔对缺氧性肺动脉收缩反应的抑制作用，提示此类药物在临床治疗中的前景。AIM: To study the effects of potassium channel opener nicorandil and potassium channel blocker CsCl on hypoxia induced contraction of pulmonary artery rings. METHODS: Rat pulmonary artery rings (PAR) were equilibrated in Krebs solution bubbled with gas mixture (0 95 N 2+0 05 CO 2) to induce hypoxic vasoconstriction. The endothelium was mechanically denuded from PAR. RESULTS: Hypoxia slowly increased resting tension of PAR. After 60 min hypoxia, the increased percentages of maximal KCl contraction (T Kmax %) in PAR with and without endothelium were 16%±4% and 18%±5% ( n =6) respectively. During normoxia, CsCl 10, 20 mmol·L -1 induced a slight increase of resting tension of PAR, but CsCl 40 mmol·L -1 caused contractile response in PAR, which was extracellular Ca 2+ dependent. However, the effects of CsCl on hypoxia induced contraction of PAR were enhanced. During hypoxia, CsCl 10 mmol·L -1 increased T Kmax % of PAR by 750%, while CsCl 20, 40 mmol·L -1 induced contractile response in PAR, the increases of T Kmax % were 354% and 17% ( n =6), respectively. In contrast, nicorandil inhibited the increased T Kmax % of PAR by hypoxia in a concentration dependent manner. Furthermore, nicorandiol (3, 10, 30 mmol·L -1 ) also inhibited the effects on hypoxia induced contraction by CsCl in a concentration dependent manner. The responses of PAR with endothelium to CsCl and nicorandil were similar to those of PAR without endothelium during normoxia and hypoxia. CONCLUSION: CsCl enhanced, but nicorandil inhibited, hypoxia induced contraction of PAR. These results suggest that the block of potassium channel affects hypoxic pulmonary vasoconstriction, which is not endothelium dependent.

关 键 词：钾通道开放剂 尼可地尔 氯化铯 缺氧 肺动脉收缩 

分 类 号：R972[医药卫生—药品]