Discordant effects of nicotine on endothelial cell proliferation, migration, and the inward rectifier potassium current

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• 作者：Kuhlmann ; Christoph Rü ; diger Wolfram ; Scharbrodt ; Wolfram ; Schaefer ; Christian Alexander ; et. al.
• 关键词：Basic fibroblast growth factor ; Nicotine ; Inward rectifier potassium current ; Endothelium ; Angiogenesis ; Nitric oxide
• 刊名：Journal of Molecular and Cellular Cardiology
• 出版年：2005
• 出版时间：February, 2005
• 年：2005
• 卷：38
• 期：2
• 页码：315-322
• 全文大小：376 K

文摘

The inward rectifier K⁺ current (K_ir) determines the resting membrane potential of endothelial cells. Basic fibroblast growth factor (bFGF) has been shown to activate K_ir and acts as angiogenic factor and vasodilator. In contrast, nicotine has been demonstrated to reduce endothelium-dependent vasorelaxation by increasing radical formation. Aim of the present study was to investigate whether nicotine modulates K_ir and if this plays a role in bFGF-mediated proliferation, migration and nitric oxide (NO)-formation of endothelial cells. Using the patch-clamp technique in cultured endothelial cells of human umbilical cord veins (HUVEC), we found characteristic K_ir, which were blocked by extracellular barium (100 μmol/l). Perfusion with nicotine (1 nmol/l–10 μmol/l) revealed a dose-dependent reduction of K_ir. The simultaneous perfusion with bFGF (50 ng/ml) and nicotine (10 μmol/l) still significantly reduced K_ir (n = 8; P < 0.01). Cell counts revealed that bFGF-mediated proliferation of HUVEC was significantly inhibited when using 1–10 μmol/l nicotine (n = 8, P < 0.01). The bFGF-induced endothelial cell migration—examined using the “Fences-Migration-Assay”—was significantly reduced by 10 μmol/l nicotine (n = 12; P < 0.05). NO-production was examined using a cGMP-Radioimmunoassay. The significant bFGF-induced increase of cGMP-levels was reduced by nicotine (n = 10; P < 0.05). Our data indicate that the modulation of K_ir seems to be an essential pathway in the antagonistic effects of nicotine on bFGF-mediated endothelial cell growth, migration and NO-formation.