Effects of Ketamine on Vascular Smooth Muscle Function

1In vitro studies were undertaken on rat aortic strips and portal vein segments to determine whether or not the amine-type anaesthetic, ketamine, can exert direct actions on vascular smooth muscle.2 Ketamine was found to inhibit development of spontaneous mechanical activity and lower basal tension. This action took place with ketamine concentrations found in anaesthetic plasma concentrations, i.e., 1 x 10(-5) to 2 x 10(-4) M.3 Ketamine (10(-5) to 10(-3) M) dose-dependently attenuated contractions induced by adrenaline, noradrenaline, angiotensin II, vasopressin and KCl. These inhibitory actions were observed with ketamine added either before or after the induced contractions.4 Ca(2+)-induced contractions of K(+)-depolarized aortae and portal veins were also attenuated, dose-dependently, by ketamine.5 In contrast to the above inhibitory actions, ketamine (2 x 10(-6) to 1 x 10(-4) M) was found to potentiate specifically 5-hydroxytryptamine(5-HT)-induced contractions of both aortic and venous smooth muscle. However, this was only observed if ketamine was added after 5-HT had initiated a contractile response.6 All of the inhibitory, as well as 5-HT-potentiating, effects were completely, and almost immediately, reversed upon washing out the anaesthetic from the organ baths.7 A variety of pharmacological antagonists failed to mimic or affect the inhibitory effects induced by ketamine.8 These data suggest that rat plasma concentrations of ketamine commonly associated with induction of surgical anaesthesia can induce, directly, relaxation and contractile potentiation of vascular muscle.9 These diverse findings may aid in explaining the well-known biphasic pressor actions of ketamine.