Korean J Physiol Pharmacol.  2016 Nov;20(6):605-611. 10.4196/kjpp.2016.20.6.605.

Facilitation of serotonin-induced contraction of rat mesenteric artery by ketamine

• Park SW
• Noh HJ
• Kim JM
• Kim B
• Cho SI
• Kim YS
• Woo NS
• Kim SH
• Bae YM

• KMID: 2364264
• DOI: http://doi.org/10.4196/kjpp.2016.20.6.605

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 (10~100 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-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.

Keyword

Blood pressure; Ketamine; Mesenteric artery; Schizophrenia; 5-HT(2A) receptor

MeSH Terms

Animals
Arteries
Blood Pressure
Humans
Hypertension
Ketamine*
Ketanserin
Mesenteric Arteries*
Models, Animal
Norepinephrine
Rats*
Receptor, Serotonin, 5-HT2A
Schizophrenia
Serotonin
Shock
Vasoconstriction
Ketamine
Ketanserin
Norepinephrine
Receptor, Serotonin, 5-HT2A
Serotonin

Figure

• 

  Fig. 1 Effects of ketamine on the tone of arterial rings in the absence and presence of 5-hydroxytryptamine (5-HT) or norepinephrine (NE).(A) Upper panel represents a typical trace showing the effect of ketamine on the arterial tone in the presence of 5-HT (200 nM). Lower panel summarizes the effect of ketamine on the arterial tone in the presence of 5-HT (100~200 nM). (B) Upper panel represents a typical trace showing the effect of ketamine on the arterial tone in the presence of NE (10 nM). Lower panel summarizes the upper panel experiments. (C) Upper panel represents a typical trace showing the effect of ketamine on the arterial tone in the absence of 5-HT and NE. Lower panel summarizes the upper panel experiments.

• 

  Fig. 2 Effect of ketamine on the concentration-response (contraction) curve (CRC) of 5-HT and NE.(A, B) CRCs of 5-HT in the absence and presence of 30 and 300 µM ketamine, respectively. (C, D) CRCs of NE in the absence and presence of 30 and 300 µM ketamine, respectively.

• 

  Fig. 3 Effects of ketanserin, anpirtoline, and BW723C86 on the ketamine-induced facilitation of vasoconstriction.(A) Ketanserine, a potent competitive inhibitor of 5-HT2A receptors, similarly shifted the CRCs of 5-HT in the absence and presence of ketamine (30 µM). (B) Anpirtoline and BW723C86, which are agonists of 5-HT1B and 5-HT2B receptors, respectively, failed to contract the mesenteric arterial rings both in the presence and in the absence of ketamine (30 µM).

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