title: Facilitation of serotonin-induced contraction of rat mesenteric artery by ketamine.
abstract: Ketamine is an anesthetic with hypertensive effects, which make it useful for patients at risk of shock. However, previousex vivostudies 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 (10~100 µM) 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 µM), 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-HT2Areceptor inhibitor, indicating that ketamine facilitated the activation of 5-HT2Areceptors. Anpirtoline and BW723C86, selective agonists of 5-HT1Band 5-HT2Breceptors, respectively, did not contract arterial rings in the absence or presence of ketamine. These results indicate that ketamine specifically enhances 5-HT2Areceptor-mediated vasoconstriction and that it is vasoconstrictive in a clinical setting. The facilitative action of ketamine on 5-HT2Areceptors 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.
authors.affiliation: Department of Emergency Medical Services, Eulji University, Seongnam 13135, Korea.
authors.forename: Sang Woong
authors.initials: SW
authors.lastname: Park
authors.affiliation: Department of Physiology, KU Open Innovation Center, Research Institute of Medical Science, Konkuk University School of Medicine, Chungju 27478, Korea.
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Noh
authors.affiliation: Department of Physiology, KU Open Innovation Center, Research Institute of Medical Science, Konkuk University School of Medicine, Chungju 27478, Korea.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Department of Physiology, KU Open Innovation Center, Research Institute of Medical Science, Konkuk University School of Medicine, Chungju 27478, Korea.
authors.forename: Bokyung
authors.initials: B
authors.lastname: Kim
authors.affiliation: Department of Physiology, KU Open Innovation Center, Research Institute of Medical Science, Konkuk University School of Medicine, Chungju 27478, Korea.
authors.forename: Sung-Il
authors.initials: SI
authors.lastname: Cho
authors.affiliation: Department of Anesthesiology, Konkuk University School of Medicine, Seoul 05030, Korea.
authors.forename: Yoon Soo
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology, Konkuk University School of Medicine, Seoul 05030, Korea.
authors.forename: Nam Sik
authors.initials: NS
authors.lastname: Woo
authors.affiliation: Department of Neurology, Kangwon National University School of Medicine, Chuncheon 24289, Korea.
authors.forename: Sung Hun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Physiology, KU Open Innovation Center, Research Institute of Medical Science, Konkuk University School of Medicine, Chungju 27478, Korea.
authors.forename: Young Min
authors.initials: YM
authors.lastname: Bae
keywords: 5-HT2A receptor; Blood pressure; Ketamine; Mesenteric artery; Schizophrenia