MAGNESIUM-SULFATE AND DIPHENYLHYDANTOIN RELAX CANINE MIDDLE CEREBRAL-ARTERY CONTRACTED WITH THE THROMBOXANE-A(2) ANALOG U46619 BY DIFFERENTMECHANISMS - IMPLICATIONS FOR THE MANAGEMENT OF ECLAMPSIA

Objectives: To investigate the relaxant effect of MgSO4 and diphenylhy dantoin on isolated canine middle cerebral artery (MCA) rings contract ed with the thromboxane-A(2) analogue U46619. Methods: Canine MCA ring s, with and without endothelium, were suspended in organ chambers for isometric tension recording. They were contracted with U46619 in the p resence of indomethacin, with and without nitro-L-arginine (NLA). Cumu lative dose-response curves were performed using MgSO4 (10(-8) M to 10 (-2) M) and diphenylhydantoin (10(-9) M to 10(-3) M). Main Outcome Mea sures: Tension at each concentration of the study drug expressed as a percentage of the maximum tension developed with U46619; area under th e concentration response curve. Results: Both MgSO4 and diphenylhydant oin relaxed the MCA rings irrespective of the presence of endothelium. Diphenylhydantoin caused an endothelium-dependent relaxation at conce ntrations above 3 x 10(-5) M, unaffected by NLA. Conclusions: MgSO4 re laxes canine MCA by a direct smooth muscle effect independent of the e ndothelium. Diphenylhydantoin causes an endothelium-dependent relaxati on of canine MCA at concentrations above 3 x 10(-5) M, unrelated to ni tric oxide. MgSO4 and diphenylhydantoin may both help to prevent seizu res in patients with eclampsia by reducing the potential for cerebral vasospasm.