Korean J Anesthesiol.  2012 Dec;63(6):533-539. 10.4097/kjae.2012.63.6.533.

Vasorelaxant mechanisms of ketamine in rabbit renal artery

• Jung I
• Jung SH

• KMID: 2236255
• DOI: http://doi.org/10.4097/kjae.2012.63.6.533

Abstract

BACKGROUND
Ketamine is a non-barbiturate anesthetic agent which has various effects on the cardiovascular system. Among them, ketamine is known for its hypotensive properties. The hypotension is thought to be mediated by a direct effect on vascular smooth muscles. This study is designed to examine the effects of ketamine on KCl- and histamine-induced contraction in isolated rabbit renal arteries.
METHODS
Endothelium-intact or -denuded smooth muscle rings were prepared and mounted in myographs for isometric tension measurements. The inhibitory effect of ketamine were investigated in smooth muscle rings precontracted with either 50 mM KCl- or 10 microM histamine.
RESULTS
Ketamine (0.1-100 microg/ml) produced similar concentration-dependent inhibition of contractile responses induced by either 50 mM KCl or 10 microM histamine. The respective IC50 values measured for ketamine following precontractions by 50 mM KCl and 10 microM histamine were 28.9 microg/ml (105.5 microM) and 26.7 microg/ml (97.5 microM). The inhibitory effect of 30 microg/ml ketamine were similarly observed after removal of endothelium or pretreatment with NG-Nitroarginine Methyl Ester (0.1 mM). The inhibitory effect of 30 microg/ml ketamine on histamine-evoked contraction was reduced by either tetraethylammonium (10 mM) or iberiotoxin, a large conductance Ca2+-activated K+ channel blocker. However, depletion of intracellular Ca2+ stores by ryanodine (10 microM) or thapsigargin (10 microM) showed no significant effect on 30 microg/ml ketamine-induced relaxation. Pre-incubation with 30 microg/ml ketamine significantly inhibited CaCl2-induced contraction at almost all ranges of concentration.
CONCLUSIONS
Ketamine-induced relaxation of rabbit renal arteries is mediated by both the activation of large conductance Ca2+-activated K+ channel and the inhibition of Ca2+ influx.

Keyword

Ca2+ influx; Ketamine; Potassium channel; Rabbit renal artery; Relaxation

MeSH Terms

Cardiovascular System
Contracts
Endothelium
Histamine
Hypotension
Inhibitory Concentration 50
Ketamine
Muscle, Smooth
Muscle, Smooth, Vascular
NG-Nitroarginine Methyl Ester
Peptides
Potassium Channels
Relaxation
Renal Artery
Ryanodine
Tetraethylammonium
Thapsigargin
Histamine
Ketamine
NG-Nitroarginine Methyl Ester
Peptides
Potassium Channels
Ryanodine
Tetraethylammonium
Thapsigargin