Magnesium sulfate and diphenylhydantoin relax canine middle cerebral artery contracted with the thromboxane-A2 analogue U46619 by different mechanisms: Implications for the management of eclampsia

Abstract

Objectives: To investigate the relaxant effect of MgSO4 and diphenylhydantoin on isolated canine middle cerebral artery (MCA) rings contracted with the thromboxane-A2 analogue U46619. Methods: Canine MCA rings, with and without endothelium, were suspended in organ chambers for isometric tension recording, they were contracted with U46619 in the presence of indomethacin, with and without nitro-L-arginine (NLA). Cumulative 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 Measures: Tension at each concentration of the study drug expressed as a percentage of the maximum tension developed with U46619; area under the concentration response curve. Results: Both MgSO4 and diphenylhydantoin relaxed the MCA rings irrespective of the presence of endothelium. Diphenylhydantoin caused an endothelium-dependent relaxation at concentrations above 3x10-5 M, unaffected by NLA. Conclusions: MgSO4 relaxes canine MCA by a direct smooth muscle effect independent of the endothelium. Diphenylhydantoin causes an endothelium-dependent relaxation of canine MCA at concentrations above 3x10-5 M, unrelated to nitric oxide. MgSO4 and diphenylhydantoin may both help to prevent seizures in patients with eclampsia by reducing the potential for cerebral vasospasm.