Kynurenine causes vasodilation and hypotension induced by activation of KCNQ-encoded voltage-dependent K+ channels
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 ameli...
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| Format: | Article |
| Language: | English |
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Elsevier
2015-09-01
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| Series: | Journal of Pharmacological Sciences |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861315001747 |
| _version_ | 1831727238682247168 |
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| author | Kensuke Sakakibara Guo-Gang Feng Jiazheng Li Takahiko Akahori Yoshitaka Yasuda Emi Nakamura Noboru Hatakeyama Yoshihiro Fujiwara Hiroyuki Kinoshita |
| author_facet | Kensuke Sakakibara Guo-Gang Feng Jiazheng Li Takahiko Akahori Yoshitaka Yasuda Emi Nakamura Noboru Hatakeyama Yoshihiro Fujiwara Hiroyuki Kinoshita |
| author_sort | Kensuke Sakakibara |
| collection | DOAJ |
| description | 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 μM). l-Kynurenine (10 μM–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 μM). Wistar rats received l-kynurenine (1 mM) iv and subsequent linopirdine (10 μM) 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. |
| first_indexed | 2024-12-21T06:25:42Z |
| format | Article |
| id | doaj.art-6902808a195946d6befa199951969fff |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-21T06:25:42Z |
| publishDate | 2015-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-6902808a195946d6befa199951969fff2022-12-21T19:13:08ZengElsevierJournal of Pharmacological Sciences1347-86132015-09-011291313710.1016/j.jphs.2015.07.042Kynurenine causes vasodilation and hypotension induced by activation of KCNQ-encoded voltage-dependent K+ channelsKensuke Sakakibara0Guo-Gang Feng1Jiazheng Li2Takahiko Akahori3Yoshitaka Yasuda4Emi Nakamura5Noboru Hatakeyama6Yoshihiro Fujiwara7Hiroyuki Kinoshita8Department of Anesthesiology, Aichi Medical University School of Medicine, 1-1 Yazako Karimata, Nagakute, Aichi 480-1195, JapanDepartment of Pharmacology, Aichi Medical University School of Medicine, 1-1 Yazako Karimata, Nagakute, Aichi 480-1195, JapanDepartment of Anesthesiology, Aichi Medical University School of Medicine, 1-1 Yazako Karimata, Nagakute, Aichi 480-1195, JapanDepartment of Anesthesiology, Aichi Medical University School of Medicine, 1-1 Yazako Karimata, Nagakute, Aichi 480-1195, JapanDepartment of Anesthesiology, Aichi Medical University School of Medicine, 1-1 Yazako Karimata, Nagakute, Aichi 480-1195, JapanDepartment of Anesthesiology, Aichi Medical University School of Medicine, 1-1 Yazako Karimata, Nagakute, Aichi 480-1195, JapanDepartment of Anesthesiology, Aichi Medical University School of Medicine, 1-1 Yazako Karimata, Nagakute, Aichi 480-1195, JapanDepartment of Anesthesiology, Aichi Medical University School of Medicine, 1-1 Yazako Karimata, Nagakute, Aichi 480-1195, JapanDepartment of Anesthesiology, Aichi Medical University School of Medicine, 1-1 Yazako Karimata, Nagakute, Aichi 480-1195, JapanKynurenine 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 μM). l-Kynurenine (10 μM–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 μM). Wistar rats received l-kynurenine (1 mM) iv and subsequent linopirdine (10 μM) 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.http://www.sciencedirect.com/science/article/pii/S1347861315001747HypotensionKynurenineVasodilationVoltage-dependent K+ channels encoded by the KCNQ gene family |
| spellingShingle | Kensuke Sakakibara Guo-Gang Feng Jiazheng Li Takahiko Akahori Yoshitaka Yasuda Emi Nakamura Noboru Hatakeyama Yoshihiro Fujiwara Hiroyuki Kinoshita Kynurenine causes vasodilation and hypotension induced by activation of KCNQ-encoded voltage-dependent K+ channels Journal of Pharmacological Sciences Hypotension Kynurenine Vasodilation Voltage-dependent K+ channels encoded by the KCNQ gene family |
| title | Kynurenine causes vasodilation and hypotension induced by activation of KCNQ-encoded voltage-dependent K+ channels |
| title_full | Kynurenine causes vasodilation and hypotension induced by activation of KCNQ-encoded voltage-dependent K+ channels |
| title_fullStr | Kynurenine causes vasodilation and hypotension induced by activation of KCNQ-encoded voltage-dependent K+ channels |
| title_full_unstemmed | Kynurenine causes vasodilation and hypotension induced by activation of KCNQ-encoded voltage-dependent K+ channels |
| title_short | Kynurenine causes vasodilation and hypotension induced by activation of KCNQ-encoded voltage-dependent K+ channels |
| title_sort | kynurenine causes vasodilation and hypotension induced by activation of kcnq encoded voltage dependent k channels |
| topic | Hypotension Kynurenine Vasodilation Voltage-dependent K+ channels encoded by the KCNQ gene family |
| url | http://www.sciencedirect.com/science/article/pii/S1347861315001747 |
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