EFFECTS OF KETAMINE ON VASCULAR SMOOTH MUSCLE FUNCTION

Abstract

1 In 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 × 10⁻⁵ to 2 × 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 Ca²⁺-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 × 10⁻⁶ to 1 × 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.