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.
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.


CONCLUSIONS
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.
Artificial Muscle Research Center, Konkuk University, Seoul, Korea.
Hyun J
HJ
Noh
Young M
YM
Bae
Seung H
SH
Park
Jae G
JG
Kim
Bokyung
B
Kim
Yoon S
YS
Kim
Seong H
SH
Kim
Sung-Il
SI
Cho
Nam S
NS
Woo
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011189:Potassium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D013152:Splanchnic Circulation / Q000187:drug effects; D013237:Stereoisomerism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents
D000778:Anesthetics, Dissociative; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D011189:Potassium Chloride; D007649:Ketamine; D015763:2-Amino-5-phosphonovalerate; D009638:Norepinephrine