Ketamine-induced relaxation in intact and skinned smooth muscles of the rabbit ear artery

1. The effects of ketamine, an intravenous anaesthetic, on the rabbit ear artery were investigated by measuring the tension in intact and saponin-treated skinned smooth-muscle fibres. 2. Ketamine dose-dependently inhibited contractions of intact smooth-muscle fibres induced by high K+ solution and by noradrenaline (NA) or histamine in Krebs solution. This drug similarly attenuated both phasic and tonic contractions induced by high K+ solution. 3. Ketamine also inhibited NA- or histamine-induced contractions in Ca2+-free solution containing 2mM EGTA, but it did not affect the caffeine-induced contraction in this solution. 4. Because the pCa-tension relationship of saponin-treated skinned smooth-muscle fibres was not affected, it can be proposed that ketamine does not have an effect on the contractile proteins. 5. In the presence of 5mM NaN3, 20 microM inositol 1,4,5-trisphosphate (InsP3) or 25mM caffeine produced a contraction in skinned smooth-muscle fibres after accumulation of Ca2+ by intracellular stores. Analysis of the InsP3- or caffeine-induced contractions indicates that ketamine does not have an effect on the Ca2+ accumulation into and Ca2+ release from the intracellular stores. 6. These results indicate that the relaxant effects produced by ketamine in the rabbit ear artery are not likely to be due to an intracellular action. The inhibitory effects of ketamine could be caused by a decrease of the Ca2+ influx through the plasma membrane or interference with the process of signal transduction between receptors on the plasma membrane and intracellular stores.