The vascular response to the K+ channel inhibitor 4-aminopyridine in hypertensive rats
The vascular response to the K+ channel inhibitor 4-aminopyridine in hypertensive rats
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DOI：
10.1016/s0014-2999(03)01555-3
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发表时间：
2003-04-18
影响因子：
5
通讯作者：
Berg, T
中科院分区：
文献类型：
--
作者：
Berg, T
K+通道抑制剂4-氨基吡啶诱导自发性高血压大鼠（SHR）血压和张力立即升高。进一步的分析强烈表明，这是由于血管平滑肌K+通道的关闭，正如之前在正常血压大鼠（WKY）中得出的结论。SHR的张力反应比WXY更大，表明通道活性增加，以补偿SHR中高总外周血管阻力。两种菌株在使用一氧化氮合酶抑制剂后反应增强，可能反映了NO- cgmp途径被消除后通道活性增加。在α(1)-肾上腺素能受体抑制和肾上腺切除术后，SHR的反应增加，而WKY的反应没有增加，但交感神经递质耗竭没有增加。使用血管紧张素AT(1)和内皮素ETA受体拮抗剂和蛋白激酶C抑制剂后也升高。这些结果表明，SHR中肾上腺儿茶酚胺、血管紧张素AT(1)和内皮素ETA激活磷脂酶C-蛋白激酶C通路，抑制4-氨基吡啶敏感的K+通道。(C) 2003 Elsevier Science B.V.版权所有
The K+ channel inhibitor 4-aminopyridine induced an immediate increase in blood pressure and tension in spontaneously hypertensive rats (SHR). Further analysis strongly suggested this to be due to closure of vascular smooth muscle K+ channels, as previously concluded for normotensive rats (WKY). The tension response was greater in SHR than WXY, suggesting an increased channel activity in order to compensate for the high total peripheral vascular resistance in SHR. The response was enhanced after nitric oxide (NO) synthase inhibitor in both strains, probably reflecting increased channel activity after elimination of the NO-cGMP pathway. The response in SHR but not WKY was increased after alpha(1)-adrenoceptor inhibition and adrenalectomy but not sympathetic nerve transmitter depletion. It increased also after angiotensin AT(1) and endothelin ETA receptor antagonists and protein kinase C inhibitor. These results indicated an increased adrenal catecholamine, angiotensin AT(1) and endothelin ETA activation of the phospholipase C-protein kinase C pathway in SHR, inhibiting the 4-aminopyridine-sensitive K+ channels. (C) 2003 Elsevier Science B.V. All rights reserved.