分析nicorandil放松和复极化机制的大鼠肠系膜动脉。
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藤原T,安格斯农协
分析nicorandil放松和复极化机制的大鼠肠系膜动脉。
Br J杂志。1996年12月,119 (8):1549 - 56。
- PubMed ID
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8982500 (在PubMed]
- 文摘
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1。nicorandil的机制导致放松分离的大鼠肠系膜小动脉安装在Mulvany肌动描记器被使用公认的组合机制研究对手。2。在动脉thromboxane-mimetic婚约,的EC50 U46619 cromakalim和levcromakalim-induced松弛曲线是由36和17倍格列本脲(3 microM)而nicorandil-induced放松的EC50影响格列本脲或亚甲蓝(10 microM)。这些对手的结合提高了nicorandil的EC50的8倍。3所示。在U46619-contracted动脉,硝苯地平(100海里)并不影响cromakalim松弛曲线,但它提高了nicorandil的EC50 5折。亚甲蓝的结合,格列本脲和硝苯地平进一步抑制nicorandil最大放松。4所示。在不同的实验中,膜电位(Em)和强迫响应同时测量。 In arteries depolarized and contracted by U46619 both nicorandil and cromakalim repolarized (delta Em, 35 mV) and relaxed (100%) the vessels. Glibenclamide (3 microM) did not alter the relaxation-concentration curve to nicorandil but reduced the maximum repolarization to delta 10.8 mV. In contrast to Em and relaxation-response curves to cromakalim were shifted to the right by glibenclamide by 30-100 fold. 5. In unstimulated arteries, nicorandil (but not cromakalim) -induced hyperpolarization was significantly antagonized by methylene blue (10 microM) (6.6 fold rightward shift) or nifedipine (100 nM) (2.6 fold). In depolarized arteries (U46619), nifedipine but not methylene blue inhibited the nicorandil-induced hyperpolarization. 6. In arteries precontracted to 50% tissue maximum by either KCl or U46619, nifedipine (100 nM) relaxed the artery but failed to repolarize the Em. Presumably voltage-operated calcium channels (VOCC) were blocked preventing contraction but the artery remained depolarized, presumably through non VOCC mechanisms. 7. These data suggest that nicorandil may relax small arteries through 3 parallel pathways, (i) NO-donor mediated stimulation of guanylate cyclase and increase in cyclic GMP, (ii) K+ATP channel opening, and (iii) nifedipine-sensitive VOCC inhibition. Em data suggest that nicorandil-induced repolarization is caused principally through opening K+ATP channels. Blockade of this hyperpolarization by glibenclamide is not sufficient to alter the relaxation, indicating dissociation of nicorandil-induced changes in membrane potential and relaxation. 8. These results highlight the 'chameleon' actions of nicorandil where there is no apparent association of Em repolarization with relaxation, in contrast to the parallel responses for cromakalim.
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