Kynurenine causes vasodilation and hypotension induced by activation of KCNQ-encoded voltage-dependent K(+) channels

Journal of Pharmacological Sciences
Kensuke SakakibaraHiroyuki Kinoshita

Abstract

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 ...Continue Reading

References

Jan 1, 1992·The Japanese Journal of Physiology·T Okuno
Oct 31, 2002·Nature Reviews. Drug Discovery·Trevor W Stone, L Gail Darlington
Dec 25, 2004·Circulation Research·Frances PlaneWilliam Cole
Oct 20, 2009·Progress in Biophysics and Molecular Biology·Eun A KoJin Han
Feb 16, 2010·The Journal of Infectious Diseases·Pierre TattevinKarin Tarte
Mar 9, 2010·Nature Medicine·Franz Hofmann
Sep 16, 2010·British Journal of Pharmacology·Fu Liang NgIain A Greenwood
Jul 19, 2011·Critical Care Medicine·Dechaboon ChangsirivathanathamrongRoland Stocker
Oct 21, 2011·Physiology·Maria Virginia SoldovieriMaurizio Taglialatela
Jan 19, 2012·British Journal of Pharmacology·Preet S ChadhaIain A Greenwood
May 18, 2012·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Isabelle WolowczukOdile Poulain-Godefroy
Nov 6, 2012·Trends in Pharmacological Sciences·Trevor W StoneL Gail Darlington
Nov 28, 2012·Hypertension·Olga ZavaritskayaRudolf Schubert

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Citations

Apr 20, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yean Chun LohMun Fei Yam
Feb 7, 2017·Experimental Biology and Medicine·Jacek BartosiewiczDariusz Pawlak
Apr 28, 2018·Clinical and Experimental Pharmacology & Physiology·Sean P NassoiyMatthias Majetschak
Feb 15, 2019·Nature·Christopher P StanleyRoland Stocker
Mar 10, 2019·Fundamental & Clinical Pharmacology·Muhammed Fatih DoganKemal Gokhan Ulusoy
Apr 6, 2019·Current Pharmaceutical Design·Emilie HitzerdA H Jan Danser
Sep 11, 2020·ESC Heart Failure·Charlotte AnderssonRamachandran S Vasan
Oct 5, 2017·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Kenneth L Byron, Lyubov I Brueggemann
Jul 3, 2020·Frontiers in Immunology·Lijie ZhaiDerek A Wainwright
Feb 3, 2021·International Journal of Molecular Sciences·Yi-Ching LoSheng-Nan Wu
Mar 4, 2021·Circulation Research·Stephanie A WortonJenny E Myers
Apr 9, 2021·Pharmacology & Therapeutics·Marta Marszalek-GrabskaWaldemar A Turski
Aug 9, 2021·Journal of Reproductive Immunology·Angela SilvanoMariarosaria Di Tommaso

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