Potassium channel openers prevent beta-amyloid toxicity in bovine vascularendothelial cells

There is increasing evidence that the cerebrovasculture may be involved in the pathology of Alzheimer's disease. Here, we report that potassium channe l openers (KCOs) inhibit dose and time dependent necrosis induced by beta-a myloid (A beta) in cultured vascular endothelia[ cells. Cell proliferation rate was assayed by a colorimetric method. A beta cytotoxicity and inhibiti on by the K-ATP channel opener diazoxide and the K-Ca channel opener NS1619 was correlated with changes in nitric oxide (NO) production. The protectiv e effects were partly blocked by potassium channel blockers. Toxicity of A beta and KCO protection was verified by histological examination of endothe lial cells with scanning electron microscopy. eNOS levels in endothelial ce lls were not changed by any of the treatments. The results suggest that dis ruption of K+ channels function may be a critical step in A beta-induced cy totoxicity in endothelial cells by alteration of NO release. (C) 2000 Elsev ier Science Ireland Ltd. All rights reserved.