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

The inward rectifier K + current (Kir) determines the resting membrane potential of endothelial cells. Basic fibroblast growth factor (bFGF) hasbeenshowntoactivateKirandactsasangiogenicfactorandvasodilator.Incontrast,nicotinehasbeendemonstratedtoreduceendotheliumdependent vasorelaxation by increasing radical formation. Aim of the present study was to investigate whether nicotine modulates Kir 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 Kir, which were blocked by extracellular barium (100 µmol/l). Perfusion with nicotine (1 nmol/l‐10 µmol/l) revealed a dose-dependent reduction of Kir. The simultaneous perfusion with bFGF (50 ng/ml) and nicotine (10 µmol/l) still significantly reduced Kir (n =8 ;P < 0.01). Cell counts revealed that bFGFmediated 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 Kir seems to be an essential pathway in the antagonistic effects of nicotine on bFGF-mediated endothelial cell growth, migration and NO-formation. © 2004 Published by Elsevier Ltd.