title: Vasorelaxant mechanisms of ketamine in rabbit renal artery.
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 µM histamine.
  
  
  RESULTS
  Ketamine (0.1-100 µg/ml) produced similar concentration-dependent inhibition of contractile responses induced by either 50 mM KCl or 10 µM histamine. The respective IC(50) values measured for ketamine following precontractions by 50 mM KCl and 10 µM histamine were 28.9 µg/ml (105.5 µM) and 26.7 µg/ml (97.5 µM). The inhibitory effect of 30 µg/ml ketamine were similarly observed after removal of endothelium or pretreatment with N(G)-Nitroarginine Methyl Ester (0.1 mM). The inhibitory effect of 30 µg/ml ketamine on histamine-evoked contraction was reduced by either tetraethylammonium (10 mM) or iberiotoxin, a large conductance Ca(2+)-activated K(+) channel blocker. However, depletion of intracellular Ca(2+) stores by ryanodine (10 µM) or thapsigargin (10 µM) showed no significant effect on 30 µg/ml ketamine-induced relaxation. Pre-incubation with 30 µg/ml ketamine significantly inhibited CaCl(2)-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 Ca(2+)-activated K(+) channel and the inhibition of Ca(2+) influx.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea.
authors.forename: Il
authors.initials: I
authors.lastname: Jung
authors.forename: Sung Hwan
authors.initials: SH
authors.lastname: Jung
keywords: Ca2+ influx; Ketamine; Potassium channel; Rabbit renal artery; Relaxation