Chi X, Sutton E T, Thomas T, Price J M
Department of Physiology and Biophysics, University of South Florida, Tampa, USA.
Neurol Res. 1999 Jun;21(4):345-51. doi: 10.1080/01616412.1999.11740942.
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.
淀粉样血管病的特征是β淀粉样肽（Aβ）沉积，可能导致阿尔茨海默病（AD）发病前的脑血管异常。Aβ对正常成纤维细胞钾（K+）通道的有害作用以及钾通道开放剂（KCOs）在神经元细胞培养中预防Aβ诱导的毒性，支持了AD患者存在异常钾通道功能的观点。我们在此报告，KCOs可保护脑和外周血管免受Aβ诱导的内皮损伤。将大鼠的大脑后动脉和主动脉环段加压，然后在与Aβ（10^-6 M）孵育前后，或在添加β淀粉样蛋白之前用KCOs预处理后，用内皮依赖性血管舒张剂乙酰胆碱使其舒张。用Aβ处理的血管表现出内皮功能障碍的特征：血管收缩增强和内皮依赖性血管舒张减弱。用KCOs预处理可显著拮抗Aβ在脑和主动脉血管段的作用。KCa和KATP通道开放剂均可提供这种保护作用。通过电子显微镜证实了Aβ引起的内皮损伤和KCOs的保护作用。钾通道阻滞剂TEA可逆转KCO的保护作用。结果表明，钾通道开放剂可防止Aβ诱导的内皮功能障碍，并且KCOs可能在治疗中风、AD和衰老等退行性脑血管疾病中发挥作用。
