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Original Article

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

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Pages 51-60 | Published online: 07 Jul 2009
 

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 MgSQ4 (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 3 10−5 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 3 10−5 M, unrelated to nitric oxide. MgSO4 and diphenylhydantoin may both help to prevent seizures in patients with eclampsia by reducing me potential for cerebral vasospasm.

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