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 vasodilation. Isolated bovine middle cerebral arteries were cut into rings to measure isometric tension development or into strips to measure radioactive 45Calcium (45Ca) uptake. Ketamine produced direct relaxation of arterial rings; the relaxation was attenuated in Ca(2+)-deficient media. Ketamine produced dose-related relaxation of arteries preconstricted with potassium, a stable thromboxane A2 analogue, or endothelin. Endothelial stripping with Triton X-100 had no effect on subsequent ketamine-induced relaxation. In Ca(2+)-deficient media containing potassium or the stable thromboxane A2 analogue, ketamine produced competitive inhibition of subsequent Ca(2+)-induced constriction. Ketamine blocked potassium- and thromboxane A2-stimulated 45Ca uptake in a dose-dependent manner, but had no effect on basal 45Ca uptake, the externally bound 45Ca content, or the volume of the 3H-sorbitol space. These results indicate that ketamine can directly dilate cerebral arteries by acting as a calcium channel antagonist; ketamine inhibits 45Ca uptake through both potential-operated (potassium) and receptor-operated (thromboxane A2) channels in cerebrovascular smooth muscle.
Wendling
W W
WW
Department of Anesthesiology, Temple University Hospital, Philadelphia, PA 19140.
Daniels
F B
FB
Chen
D
D
Harakal
C
C
Carlsson
C
C
D000818:Animals; D002118:Calcium / Q000493:pharmacokinetics / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D002132:Calcium Radioisotopes; D002417:Cattle; D002536:Cerebral Arteries / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D014661:Vasoconstriction; D014664:Vasodilation; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D016232:Endothelins; D005229:Fatty Acids, Monounsaturated; D014665:Vasodilator Agents; D007649:Ketamine; C032408:SQ 26536; D011188:Potassium; D002118:Calcium