The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Facilitation of serotonin-induced contraction of rat mesenteric artery by ketamine

  • Park, Sang Woong (Department of Emergency Medical Services, Eulji University) ;
  • Noh, Hyun Ju (Department of Physiology, KU Open Innovation Center, Research Institute of Medical Science, Konkuk University School of Medicine) ;
  • Kim, Jung Min (Department of Physiology, KU Open Innovation Center, Research Institute of Medical Science, Konkuk University School of Medicine) ;
  • Kim, Bokyung (Department of Physiology, KU Open Innovation Center, Research Institute of Medical Science, Konkuk University School of Medicine) ;
  • Cho, Sung-Il (Department of Physiology, KU Open Innovation Center, Research Institute of Medical Science, Konkuk University School of Medicine) ;
  • Kim, Yoon Soo (Department of Anesthesiology, Konkuk University School of Medicine) ;
  • Woo, Nam Sik (Department of Anesthesiology, Konkuk University School of Medicine) ;
  • Kim, Sung Hun (Department of Neurology, Kangwon National University School of Medicine) ;
  • Bae, Young Min (Department of Physiology, KU Open Innovation Center, Research Institute of Medical Science, Konkuk University School of Medicine)
  • Received : 2016.04.22
  • Accepted : 2016.08.15
  • Published : 2016.11.01
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Abstract

Ketamine is an anesthetic with hypertensive effects, which make it useful for patients at risk of shock. However, previous ex vivo studies reported vasodilatory actions of ketamine in isolated arteries. In this study, we reexamined the effects of ketamine on arterial tones in the presence and absence of physiological concentrations of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) by measuring the isometric tension of endothelium-denuded rat mesenteric arterial rings. Ketamine little affected the resting tone of control mesenteric arterial rings, but, in the presence of 5-HT (100~200 nM), ketamine ($10{\sim}100{\mu}M$) markedly contracted the arterial rings. Ketamine did not contract arterial rings in the presence of NE (10 nM), indicating that the vasoconstrictive action of ketamine is 5-HT-dependent. The concentration-response curves (CRCs) of 5-HT were clearly shifted to the left in the presence of ketamine ($30{\mu}M$), whereas the CRCs of NE were little affected by ketamine. The left shift of the 5-HT CRCs caused by ketamine was reversed with ketanserin, a competitive 5-$HT_{2A}$ receptor inhibitor, indicating that ketamine facilitated the activation of 5-$HT_{2A}$ receptors. Anpirtoline and BW723C86, selective agonists of 5-$HT_{1B}$ and 5-$HT_{2B}$ receptors, respectively, did not contract arterial rings in the absence or presence of ketamine. These results indicate that ketamine specifically enhances 5-$HT_{2A}$ receptor-mediated vasoconstriction and that it is vasoconstrictive in a clinical setting. The facilitative action of ketamine on 5-$HT_{2A}$ receptors should be considered in ketamine-induced hypertension as well as in the pathogenesis of diseases such as schizophrenia, wherein experimental animal models are frequently generated using ketamine.

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