Azelnidipine Attenuates The Oxidative And Nf Kappa B Pathways In Amyloid-Beta-Stimulated Cerebral Endothelial Cells

Cerebral amyloid angiopathy (CAA), a condition depicting cerebrovascular accumulation of amyloid beta-peptide (A beta), is a common pathological manifestation in Alzheimer's disease (AD). In this study, we investigated the effects of Azelnidipine (ALP), a dihydropyridine calcium channel blocker known for its treatment of hypertension, on oligomeric A beta (oA beta)-induced calcium influx and its downstream pathway in immortalized mouse cerebral endothelial cells (bEND3). We found that ALP attenuated oA beta-induced calcium influx, superoxide anion production, and phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and calcium-dependent cytosolic phospholipase A(2) (cPLA(2)). Both ALP and cPLA(2) inhibitor, methylarachidonyl fluorophosphate (MAFP), suppressed oA beta-induced translocation of NF kappa B p65 subunit to nuclei, suggesting that cPLA(2) activation and calcium influx are essential for oA beta-induced NF kappa B activation. In sum, our results suggest that calcium channel blocker could be a potential therapeutic strategy for suppressing oxidative stress and inflammatory responses in-stimulated microvasculature in AD.