LAUSR

Disruption of the blood‐brain barrier associated with endothelial dysfunction is an important hallmark of Parkinson's disease (PD). 6‐Hydroxydopamine (6‐OHDA) is a synthetic dopamine derivate often used to model PD as it results in retrograde degeneration of striatal dopaminergic (DA) terminals. Presently, the effects of 6‐OHDA on endothelial dysfunction remain unknown. Using a 6‐OHDA rodent model of PD, we found that administration of 6‐OHDA could increase the expression of endothelial adhesion molecules, such as intercellular adhesion molecule 1 (ICAM‐1), vascular cell adhesion molecule 1 (VCAM‐1), and E‐selectin. An in vitro study displayed that treatment with 6‐OHDA increased the release of these molecules in human brain microvascular endothelial cells in a dose‐dependent manner. Correspondingly, 6‐OHDA significantly increased attachment of THP‐1 monocytes to brain endothelial cells. In addition, real‐time polymerase chain reaction and enzyme‐linked immunosorbent assay results indicated that 6‐OHDA elevated the production of proinflammatory cytokines, such as interleukin‐1β, interleukin‐6, and tumor necrosis factor‐α. Furthermore, 6‐OHDA treatment increased the expression of cyclooxygenase‐2 and inducible nitric oxide synthase, as well as the production of prostaglandin E2 and nitric oxide. Importantly, 6‐OHDA elevated the transcriptional activity of NF‐кB by increasing the phosphorylation, degradation, and subsequent nuclear translocation of p65. Mechanistically, the angiotensin II type 1 receptor was found to mediate 6‐OHDA‐induced endothelial dysfunction. Our findings suggest that 6‐OHDA‐induced endothelial inflammation may play an important role in the pathogenesis of PD. © 2017 IUBMB Life, 69(11):887–895, 2017