Ca(2+)激活的钾通道在体内乙酰胆碱诱导的基底动脉扩张中的作用。

Role of Ca(2+)-activated K+ channels in acetylcholine-induced dilatation of the basilar artery in vivo.

作者信息

Kitazono T, Ibayashi S, Nagao T, Fujii K, Fujishima M

机构信息

Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.

出版信息

Br J Pharmacol. 1997 Jan;120(1):102-6. doi: 10.1038/sj.bjp.0700880.

DOI:10.1038/sj.bjp.0700880

PMID:9117083

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1564353/

Abstract

We tested the hypothesis that activation of large conductance calcium-activated potassium channels is involved in dilator responses of the basilar artery to acetylcholine in vivo. Using a cranial window in anaesthetized rats, we examined responses of the basilar artery to acetylcholine. 2. Topical application of acetylcholine (10(-6) and 10(-5) M) increased diameter of the basilar artery from 238 +/- 7 microns to 268 +/- 7 and 288 +/- 7 microns, respectively (P < 0.05 vs. baseline diameter). Iberiotoxin (10(-8) M), an inhibitor of large conductance calcium-activated potassium channels, did not affect baseline diameter of the basilar artery. In the presence of 10(-8) M iberiotoxin, 10(-6) and 10(-5) M acetylcholine increased diameter of the basilar artery from 239 +/- 7 microns to 246 +/- 7 and 261 +/- 7 microns, respectively. Thus, iberiotoxin attenuated acetylcholine-induced dilatation of the basilar artery (P < 0.05). 3. Sodium nitroprusside (10(-7) and 10(-6) M) increased diameter of the basilar artery from 242 +/- 9 microns to 310 +/- 12 and 374 +/- 13 microns, respectively (P < 0.05 vs. baseline diameter). In the presence of iberiotoxin (10(-8) M), sodium nitroprusside (10(-7) and 10(-6) M) increased diameter of the basilar artery from 243 +/- 6 microns to 259 +/- 9 and 311 +/- 12 microns, respectively. Thus, iberiotoxin attenuated dilator responses of the basilar artery to sodium nitroprusside (P < 0.05). 4. Iberiotoxin partly inhibited dilator responses of the basilar artery to forskolin, a direct activator of adenylate cyclase, but did not affect vasodilatation produced by levcromakalim, a potassium channel opener. 5. These results suggest that dilator responses of the basilar artery to acetylcholine and sodium nitroprusside are mediated, in part, by activation of large conductance calcium-activated potassium channels. Because both acetylcholine and sodium nitroprusside have been shown to activate guanylate cyclase via nitric oxide, activation of large conductance calcium-activated potassium channels may be one of the major mechanisms by which cyclic GMP causes dilatation of the basilar artery in vivo.

摘要

我们验证了一个假说，即大电导钙激活钾通道的激活参与了体内基底动脉对乙酰胆碱的舒张反应。在麻醉大鼠中使用颅骨开窗法，我们检测了基底动脉对乙酰胆碱的反应。2. 局部应用乙酰胆碱（10⁻⁶和10⁻⁵ M）可使基底动脉直径分别从238±7微米增加到268±7微米和288±7微米（与基线直径相比，P<0.05）。大电导钙激活钾通道抑制剂iberiotoxin（10⁻⁸ M）不影响基底动脉的基线直径。在存在10⁻⁸ M iberiotoxin的情况下，10⁻⁶和10⁻⁵ M乙酰胆碱分别使基底动脉直径从239±7微米增加到246±7微米和261±7微米。因此，iberiotoxin减弱了乙酰胆碱诱导的基底动脉舒张（P<0.05）。3. 硝普钠（10⁻⁷和10⁻⁶ M）分别使基底动脉直径从242±9微米增加到310±12微米和374±13微米（与基线直径相比，P<0.05）。在存在iberiotoxin（10⁻⁸ M）的情况下，硝普钠（10⁻⁷和10⁻⁶ M）分别使基底动脉直径从243±6微米增加到259±9微米和311±12微米。因此，iberiotoxin减弱了基底动脉对硝普钠的舒张反应（P<0.05）。4. Iberiotoxin部分抑制了基底动脉对腺苷酸环化酶直接激活剂福斯高林的舒张反应，但不影响钾通道开放剂左芬咖烷产生的血管舒张。5. 这些结果表明，基底动脉对乙酰胆碱和硝普钠的舒张反应部分是由大电导钙激活钾通道的激活介导的。由于乙酰胆碱和硝普钠均已被证明可通过一氧化氮激活鸟苷酸环化酶，大电导钙激活钾通道的激活可能是环磷酸鸟苷在体内引起基底动脉舒张的主要机制之一。