کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2533501 | 1559057 | 2010 | 6 صفحه PDF | دانلود رایگان |
Decrease in endothelial nitric oxide synthase (eNOS) expression is one of the adverse outcomes of endothelial dysfunction. Tumor necrosis factor-α (TNF-α) is known to decrease eNOS expression and is an important mediator of endothelial dysfunction. We hypothesized that an angiotensin II type 1 (AT1) receptor blocker would improve endothelial function via not only inhibition of the angiotensin II signaling but also inhibition of the TNF-α-mediated signaling. Therefore we investigated whether an AT1 receptor blocker would restore the TNF-α-induced decrease in eNOS expression in cultured human umbilical vein endothelial cells (HUVEC). Pretreatment of HUVEC with an antioxidant (superoxide dismutase, α-tocopherol) or AT1 receptor blockers (olmesartan or candesartan) restored the TNF-α-dependent reduction of eNOS. The AT1 receptor blocker decreased the TNF-α-dependent increase of 8-isoprostane. The superoxide dismutase activities in HUVEC were stable during AT1 receptor blocker treatment, and the AT1 receptor blocker did not scavenge superoxide directly. The AT1 receptor blocker also decreased TNF-α-induced phosphorylation of IκBα and cell death. These results suggest that AT1 receptor blockers are able to ameliorate TNF-α-dependent eNOS reduction or cell injury by inhibiting superoxide production or nuclear factor-κB activation.
Journal: European Journal of Pharmacology - Volume 636, Issues 1–3, 25 June 2010, Pages 36–41