Effects of ethosuximide on the cerebral vasculature and hemodynamics of rats

The development of epileptogenic activity has been proven to be closely related to changes in cerebral blood flow. This study was designed to examine the effects of ethosuximide, a widely used anticonvulsant drug, on cerebral hemodynamics. White Wistar rats were treated (p.o.) with 100 mg/kg b.w. ethosuximide. Three hours after administration, changes in cerebral blood flow due to vasodilation were recorded by means of angiography. Using the single sucrose gap method it was found that ethosuximide caused hyperpolarization of smooth muscle sample from rat internal carotid artery by 5.4 +/- 1.6 mV. The hyperpolarization was related to relaxation of smooth muscle tissue of vessels, which was recorded isometrically. Ethosuximide significantly depressed vascular reactions to the vasoconstrictive agents noradrenaline and serotonin. Ethosuximide-induced reaction was not significantly influenced by the Ca2+ antagonist verapamil, but was reduced by caffeine (10(-4) M) and apamine (5.10(-6) M), the latter being a blocker of Ca2+ -dependent K+ channels. The experimental data strongly suggest that changes in bioelectric and contractile activity of arterial smooth muscle samples are a result of Ca2+ -dependent K+ efflux, provoked by calcium which has been derived from intracellular Ca2+ store. These results show that ethosuximide-induced changes in cerebral blood flow are caused by reduced reactivity of smooth muscle tissue and vascular dilatation.