Kynurenine causes vasodilation and hypotension induced by activation of KCNQ-encoded voltage-dependent K+ channels
Kynurenine causes vasodilation and hypotension induced by activation of KCNQ-encoded voltage-dependent K+ channels
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DOI：
10.1016/j.jphs.2015.07.042
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发表时间：
2015-09-01
影响因子：
3.5
通讯作者：
Kinoshita, Hiroyuki
中科院分区：
文献类型：
--
作者：
Sakakibara, Kensuke;Feng, Guo-Gang;Kinoshita, Hiroyuki
犬尿氨酸是动物和人类败血症中低血压的潜在促成因素。本研究旨在研究KCNQ基因家族编码的电压依赖性K+通道（Kv 7通道）是否介导犬尿氨酸的血管扩张作用，以及这些通道的调节是否改善该化合物引起的低血压。采用大鼠腹主动脉和肠系膜动脉或无内皮的人网膜动脉。将一些环与选择性Kv 7通道抑制剂linopirdine（10 μ M）孵育。L-犬尿氨酸（10 μ M-1 mM）诱导大鼠腹主动脉和肠系膜动脉以及人网膜动脉的浓度依赖性松弛，而利诺吡啶取消了松弛。L-犬尿氨酸（1 mM）产生血管平滑肌超极化，这是逆转的利诺吡啶（10 μ M）。Wistar大鼠接受L-犬尿氨酸（1 mM）静脉注射，随后在3%七氟烷吸入下静脉注射利诺吡啶（10 μ M）。犬尿氨酸iv引起低血压，而利诺吡啶iv部分逆转it. In结论，犬尿氨酸扩张动脉从大鼠以及人类通过血管平滑肌中的Kv 7通道。在大鼠中，这种色氨酸代谢物导致低血压，这部分地被Kv 7通道抑制所抵消。这些结果表明，Kv 7通道的调节可能是一种新的策略，治疗犬尿氨酸引起的低血压。(C)2015日本药理学会。Elsevier B. V.代表日本药理学会制作和主办。
Kynurenine is a potential contributor to hypotension in animal and human sepsis. The present study was designed to examine whether the voltage-dependent K+ channels encoded by the KCNQ gene family (Kv7 channels) mediate vasodilator effects of kynurenine and whether modulation of these channels ameliorates hypotension caused by this compound. Rat aortas and mesenteric arteries or human omental arteries without endothelium were used. Some rings were incubated with the selective Kv7 channel inhibitor linopirdine (10 mu M). L-Kynurenine (10 mu M-1 mM) induced concentration-dependent relaxation in rat aortas and mesenteric arteries as well as human omental arteries, whereas linopirdine abolished the relaxation. L-Kynurenine (1 mM) produced hyperpolarization of vascular smooth muscle, which was reversed by linopirdine (10 mu M). Wistar rats received L-kynurenine (1 mM) iv and subsequent linopirdine (10 mu M) iv under 3% sevoflurane inhalation. L-Kynurenine iv caused hypotension, whereas linopirdine iv partially reversed it. In conclusion, kynurenine dilates arteries from rats as well as humans via Kv7 channels in the vascular smooth muscle. In rats, this tryptophan metabolite causes hypotension, which is partly counteracted by Kv7 channel inhibition. These results suggest that modulation of Kv7 channels may be a novel strategy to treat hypotension induced by the kynurenine. (C) 2015 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.