PMID- 19352184 OWN - NLM STAT- MEDLINE DCOM- 20090915 LR - 20141120 IS - 1365-2346 (Electronic) IS - 0265-0215 (Linking) VI - 26 IP - 8 DP - 2009 Aug TI - The vasodilatory effect of ketamine is independent of the N-methyl-D-aspartate receptor: lack of functional N-methyl-D-aspartate receptors in rat mesenteric artery smooth muscle. PG - 676-82 LID - 10.1097/EJA.0b013e32832a1704 [doi] AB - BACKGROUND AND OBJECTIVE: Ketamine, which is a general anaesthetic that induces a dissociative anaesthesia, acts by blocking the N-methyl-D-aspartate receptor (NMDAr) in the brain. Although ketamine elevates blood pressure under the clinical setting, the in-vitro effect of ketamine is vasodilatory. However, it is not clear yet whether the vasodilation by ketamine involves functions of the NMDAr. Therefore, we examined whether the NMDAr is functional in vascular smooth muscle and whether the vasodilatory effect of ketamine is associated with the NMDAr. METHODS: We measured isometric tension of endothelium-denuded arterial rings from rat mesentery. The relaxing effects of ketamine, after rings were precontracted with noradrenaline (10 mumol l) or high KCl (70 mmol l), were examined. The effects of DL-2-amino-5-phosphonopentanoic acid (AP-5), a competitive NMDAr blocker that is structurally distinct from ketamine, were also examined. The relaxing effects of ketamine in the presence of AP-5 were compared with those in the absence of AP-5. The effects of NMDAr agonists N-methyl-D-aspartate and glutamate were analysed in order to examine the existence of a functional NMDAr. RESULTS: Both S(+)-ketamine and racemic(+/-)-ketamine, with similar potencies and efficacies and in a concentration-dependent manner, relaxed the precontracted arterial rings. However, AP-5 neither relaxed the arteries nor affected the vasodilatory actions of ketamine. N-methyl-D-aspartate and glutamate (0.01-1 mmol l) had negligible effects on isometric tension under the resting or precontracted condition. CONCLUSION: These results suggest that the NMDAr is not functional in vascular smooth muscle, and the vasodilatory action of ketamine is independent of the NMDAr in the rat mesenteric artery. FAU - Noh, Hyun J AU - Noh HJ AD - Artificial Muscle Research Center, Konkuk University, Seoul, Korea. FAU - Bae, Young M AU - Bae YM FAU - Park, Seung H AU - Park SH FAU - Kim, Jae G AU - Kim JG FAU - Kim, Bokyung AU - Kim B FAU - Kim, Yoon S AU - Kim YS FAU - Kim, Seong H AU - Kim SH FAU - Cho, Sung-Il AU - Cho SI FAU - Woo, Nam S AU - Woo NS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Eur J Anaesthesiol JT - European journal of anaesthesiology JID - 8411711 RN - 0 (Anesthetics, Dissociative) RN - 0 (Excitatory Amino Acid Antagonists) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 0 (Vasoconstrictor Agents) RN - 0 (Vasodilator Agents) RN - 660YQ98I10 (Potassium Chloride) RN - 690G0D6V8H (Ketamine) RN - 76726-92-6 (2-Amino-5-phosphonovalerate) RN - X4W3ENH1CV (Norepinephrine) SB - IM MH - 2-Amino-5-phosphonovalerate/pharmacology MH - Anesthetics, Dissociative/*pharmacology MH - Animals MH - Excitatory Amino Acid Antagonists/*pharmacology MH - In Vitro Techniques MH - Isometric Contraction/drug effects MH - Ketamine/*pharmacology MH - Male MH - Mesenteric Arteries/*drug effects/metabolism MH - Muscle Contraction/drug effects/physiology MH - Muscle, Smooth, Vascular/*drug effects/metabolism MH - Norepinephrine/antagonists & inhibitors/pharmacology MH - Potassium Chloride/antagonists & inhibitors/pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, N-Methyl-D-Aspartate/*drug effects MH - Splanchnic Circulation/drug effects MH - Stereoisomerism MH - Vasoconstrictor Agents/pharmacology MH - *Vasodilator Agents EDAT- 2009/04/09 09:00 MHDA- 2009/09/16 06:00 CRDT- 2009/04/09 09:00 PHST- 2009/04/09 09:00 [entrez] PHST- 2009/04/09 09:00 [pubmed] PHST- 2009/09/16 06:00 [medline] AID - 10.1097/EJA.0b013e32832a1704 [doi] PST - ppublish SO - Eur J Anaesthesiol. 2009 Aug;26(8):676-82. doi: 10.1097/EJA.0b013e32832a1704.