Role of calcium-activated K+ channels in vasodilation induced by nitroglycerine, acetylcholine and nitric oxide.
Role of calcium-activated K+ channels in vasodilation induced by nitroglycerine, acetylcholine and nitric oxide.
复制标题
钙激活钾离子通道在硝化甘油、乙酰胆碱和一氧化氮诱导的血管舒张中的作用。
DOI：
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发表时间：
1993
影响因子：
3.5
通讯作者：
K. Meisheri
中科院分区：
文献类型：
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作者：
S. Khan;W. Mathews;K. Meisheri
本文比较了硝酸甘油（NTG）、乙酰胆碱（ACh）和一氧化氮（NO）对ATP敏感性钾通道（KATP）阻断剂格列本脲（Glyburide）、钙激活钾通道（KCa）阻断剂卡波毒素（ChTX）和伊比利亚毒素（IbTX）的敏感性。用5 μ M去甲肾上腺素（NE）、ACh（0.01-1 μ M）、NTG（0.01-5 μ M）和NO（0.075-2.7 μ M）预收缩离体兔肠系膜动脉（RMA），产生剂量依赖性的血管舒张作用。格列本脲（0.5 μ M）对ACh、NTG或NO的舒张剂量-反应曲线（DRC）无显著影响。相反，格列本脲完全消除了已知KATP开放剂吡那地尔的舒张DRC。ChTX（10或100 nM）对ACh、NTG和NO均能抑制舒张性DRC。在所有情况下，ChTX使舒张性DRC向右移动，并抑制最大反应。另一种有效的KCa阻断剂lbTX（20 nM）也显著抑制DRG对NTG、ACh和NO的舒张反应，并抑制对SNP的最大舒张反应。ChTX和lbTX的影响是选择性的，他们不抑制松弛吡那地尔和毛喉素。最后，观察到使用80 mM K+作为收缩刺激以类似于KCa阻断剂的方式抑制NTG舒张。总之，这些数据为KCa激活在NTG、SNP、ACh和NO引起的血管舒张中起重要作用的假设提供了有力的支持。（250字处删节）
A comparative analysis was carried out of the sensitivities of in vitro vasorelaxations by nitroglycerine (NTG), acetylcholine (ACh) and nitric oxide (NO) to blockade by glyburide, a blocker of ATP-sensitive K+ channels (KATP), as well as to blockade by charybdotoxin (ChTX) and iberiotoxin (lbTX), potent blockers of calcium-activated K+ channels (KCa). In the isolated rabbit mesenteric artery (RMA) precontracted with 5 microM norepinephrine (NE), ACh (0.01-1 microM), NTG (0.01-5 microM) and NO (0.075-2.7 microM) produced a dose-dependent vasodilation. Glyburide (0.5 microM) had no significant effect on relaxation dose-response curves (DRCs) to ACh, NTG or NO. In contrast, glyburide completely abolished the relaxation DRC by pinacidil, a known KATP opener. ChTX (10 or 100 nM) caused an inhibition of relaxation DRCs to ACh, NTG and NO. In all cases, ChTX shifted the relaxation DRC to the right and depressed the maximal response. Another potent KCa blocker, lbTX (20 nM) also significantly inhibited relaxation DRCs to NTG, ACh and NO and inhibited maximal relaxation response to SNP. The effects of ChTX and lbTX were selective; they did not inhibit relaxations by pinacidil and forskolin. Finally, it was observed that the use of 80 mM K+ as a contractile stimulus inhibited NTG relaxations in a manner similar to the KCa blockers. Collectively, these data provide strong support for the hypothesis that the activation of KCa plays an important role in mediating the vasorelaxation caused by NTG, SNP, ACh and NO.(ABSTRACT TRUNCATED AT 250 WORDS)