The protective effect of K+ channel openers on beta-amyloid induced cerebrovascular endothelial dysfunction.
Neurol Res
; 21(4): 345-51, 1999 Jun.
Article
em En
| MEDLINE
| ID: mdl-10406005
ABSTRACT
Amyloid angiopathy is characterized by amyloid beta-peptide (A beta) deposition and may contribute to the cerebrovascular abnormalities that precede the onset of Alzheimer's Disease (AD). That aberrant potassium (K+) channel function occurs in AD patients is supported by deleterious effects of A beta on normal fibroblast K+ channels and prevention of A beta-induced toxicity by potassium channel openers (KCOs) in neuronal cell culture. We report here that KCOs protect cerebral and peripheral vessels against the endothelial damage induced by A beta. Pressurized posterior cerebral artery and aortic ring segments from the rat were constricted and then relaxed with the endothelium-dependent vasodilator acetylcholine before and after incubation with A beta (10(-6) M), or pre-treatment with KCOs before the addition of beta-amyloid. Vessels treated with A beta exhibited features of endothelial dysfunction enhanced vasoconstriction and diminished endothelium-dependent vasodilation. Pre-treatment with KCOs significantly antagonized the A beta effect in both cerebral and aortic vessel segments. This protection was provided by both KCa and KATP channel openers. Endothelial damage by A beta and protection by KCOs was verified by electron microscopy. The K+ channel blocker, TEA, reversed the protective effect of KCO. The results suggest that potassium channel openers protect against A beta induced endothelial dysfunction and that KCOs may have a role in the treatment of degenerative cerebrovascular disease as seen in stroke, AD and aging.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Endotélio Vascular
/
Canais de Potássio
/
Peptídeos beta-Amiloides
/
Citoproteção
Limite:
Animals
Idioma:
En
Revista:
Neurol Res
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Estados Unidos