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钾通道开放剂克罗卡林和硫酸米诺地尔对血管平滑肌作用的比较。

Comparison of the effects of the K(+)-channel openers cromakalim and minoxidil sulphate on vascular smooth muscle.

作者信息

Wickenden A D, Grimwood S, Grant T L, Todd M H

机构信息

ICI Pharmaceuticals, Bioscience Department II, Alderley Park, Macclesfield, Cheshire.

出版信息

Br J Pharmacol. 1991 May;103(1):1148-52. doi: 10.1111/j.1476-5381.1991.tb12315.x.

Abstract

1 The actions of the potassium channel openers, cromakalim and minoxidil sulphate, were compared in a range of isolated blood vessel preparations. 2 Cromakalim and minoxidil sulphate inhibited spontaneous mechanical activity of the guinea-pig portal vein and relaxed the noradrenaline precontracted rat aorta with similar potency. In contrast, minoxidil sulphate was less potent than cromakalim in inhibiting spontaneous activity in the rat portal vein and was essentially inactive in the noradrenaline precontracted rat mesenteric artery and rabbit aorta. 3 Minoxidil sulphate did not antagonize the effects of cromakalim in the rabbit aorta indicating it was not acting as a partial 'agonist'. 4 Charybdotoxin, noxiustoxin and rubidium failed to discriminate between cromakalim and minoxidil sulphate indicating that the apparently selective effects of minoxidil sulphate were not mediated by either Ca(2+)-activated potassium channels, delayed rectifiers or rubidium impermeable potassium channels. 5 Glibenclamide antagonized the effects of cromakalim in an apparently competitive manner whereas the effects of minoxidil sulphate were antagonized in a non-competitive manner. The involvement of subtypes of ATP-sensitive potassium channels is discussed.

摘要
  1. 在一系列离体血管制剂中比较了钾通道开放剂色满卡林和硫酸米诺地尔的作用。2. 色满卡林和硫酸米诺地尔抑制豚鼠门静脉的自发机械活动,并以相似的效力松弛去甲肾上腺素预收缩的大鼠主动脉。相比之下,硫酸米诺地尔在抑制大鼠门静脉自发活动方面的效力低于色满卡林,并且在去甲肾上腺素预收缩的大鼠肠系膜动脉和兔主动脉中基本无活性。3. 硫酸米诺地尔不拮抗色满卡林在兔主动脉中的作用,表明它不是作为部分“激动剂”起作用。4. 蝎毒素、诺蝎毒素和铷不能区分色满卡林和硫酸米诺地尔,表明硫酸米诺地尔明显的选择性作用不是由钙激活钾通道、延迟整流器或铷不可渗透钾通道介导的。5. 格列本脲以明显竞争性的方式拮抗色满卡林的作用,而硫酸米诺地尔的作用则以非竞争性方式被拮抗。讨论了ATP敏感性钾通道亚型的参与情况。

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The individual enantiomers of cis-cromakalim possess K+ channel opening activity.
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