Abstract:The vasodilation mechanism induced by ketamine was investigated in isolated smooth muscle strips of rabbit portal veins. Ketamine inhibited both the phasic and tonic components of K+‐induced contraction at concentrations greater than 500 μM and 100 μM, respectively. This effect was reversible and concentration‐dependent with concentrations up to 1 mM. These effects were similar to those producd by verapamil. In the presence of 60 mM K+, application of Ca2+(2.5 mM) in the perfusing solution caused tonic contraction of the smooth muscle, and ketamine at concentrations larger than 10 μM strongly inhibited this Ca2+‐induced contraction. Ketamine (100 μM) also inhibited the K+‐induced contractions significantly in the absence and presence of guanethidine, tetrodotoxin and propranolol. Ketamine produced similar concentration‐dependent relaxations in the tissues with and without endothelium. These results indicate that in rabbit portal vein, vasodilation produced by ketamine is not endothelium‐dependent but is likely to be due to blockade of the voltage‐gated influx of e