Physiological levels ofβ-amyloid induce cerebral vessel dysfunction and reduce endothelial nitric oxide production
| Autor: | Xuedong Chi, Gary Hellermann, Joel M. Price, E. Truitt Sutton |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
medicine.medical_specialty
Programmed cell death Endothelium Vasodilation Nitric Oxide Brain Ischemia Nitric oxide Rats Sprague-Dawley chemistry.chemical_compound Alzheimer Disease Internal medicine medicine Animals Senile plaques Cells Cultured Amyloid beta-Peptides Cell Death Dose-Response Relationship Drug biology General Medicine Anatomy Cerebral Arteries Acetylcholine Rats Endothelial stem cell Nitric oxide synthase Cerebrovascular Disorders Endocrinology medicine.anatomical_structure Neurology chemistry Vasoconstriction Cerebrovascular Circulation biology.protein Endothelium Vascular Neurology (clinical) medicine.drug |
| Zdroj: | Neurological Research. 23:506-512 |
| ISSN: | 1743-1328 0161-6412 |
| DOI: | 10.1179/016164101101198758 |
| Popis: | beta-amyloid (A beta), the major component of senile plaques in Alzheimer's disease (AD), normally circulates in the blood at nanomolar levels but is elevated in AD. Previous studies have found that high concentrations (10(-5)-10(-4) M) of A beta result in neuronal cell death. Here we show that physiological levels of soluble A beta can induce dysfunction in perfused rat cerebral vessels and in cultured endothelial cells. At concentrations of 10(-9)-10(-6) M, A beta induced a significant concentration-dependent reduction of NO production in endothelial cells. At 10(-8) M, A beta significantly decreased the sensitivity of cerebral vessels to acetylcholine (ACh), an endothelium dependent vasodilator. At 10(-7) M and higher concentrations, A beta significantly reduced the maximum response of vessels to ACh, and induced significant endothelial cell death. A beta (10(-9)-10(-5) M) did not cause any detectable change in nitric oxide synthase levels. The results suggest that a modest increase in the concentration of A beta above its normal physiological level in the circulation, as found in the early stages of AD, results in decreased NO production and vessel sensitivity to endothelium-dependent vasodilation that could lead to constricted blood vessels and ischemia in the surrounding tissue. Further increases in A beta concentration, which may occur in the later stages of AD, result in cell death and decreased maximum vasodilator response of cerebral vessels. |
| Databáze: | OpenAIRE |
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