KETAMINE DIRECTLY DILATES BOVINE CEREBRAL-ARTERIES BY ACTING AS A CALCIUM-ENTRY BLOCKER

This in vitro study was performed to determine the role of calcium in ketamine-induced cerebral vasodilatation. Isolated bovine middle cereb ral arteries were cut into rings to measure isometric tension developm ent or into strips to measure radioactive Calcium-45 (Ca-45) uptake. K etamine produced direct relaxation of arterial rings; the relaxation w as attenuated in Ca2+-deficient media. Ketamine produced dose-related relaxation of arteries preconstricted with potassium, a stable thrombo xane A2 analogue, or endothelin. Endothelial stripping with Triton X-1 00 had no effect on subsequent ketamine-induced relaxation. In Ca2+-de ficient media containing potassium or the stable thromboxane A2 analog ue, ketamine produced competitive inhibition of subsequent Ca2+-induce d constriction. Ketamine blocked potassium- and thromboxane A2-stimula ted Ca-45 uptake in a dose-dependent manner, but had no effect on basa l Ca-45 uptake, the externally bound Ca-45 content, or the volume of t he H-3-sorbitol space. These results indicate that ketamine can direct ly ditate cerebral arteries by acting as a calcium channel antagonist; ketamine inhibits Ca-45 uptake through both potential-operated (potas sium) and receptor-operated (thromboxane A2) channels in cerebrovascul ar smooth muscle.