Nicotine inhibits large conductance Ca2 + -activated K+ channels and the NO/-cGMP signaling pathway in cultured human endothelial cells

Objective. The effects of nicotine on endothelium-dependent vasorelaxation mediated by nitric oxide (NO) are controversial. Since endothelial NO synthesis has been shown to depend on the activity of large conductance Ca2 + -activated K+ channels (BKCa), the present study investigated whether nicotine alters BKCa single channel activity induced by the K+ channel opener NS1619, and to examine a possible interaction with the endothelial NO generation. Design. The patch-clamp technique was used to examine the BKCa activity. NO production was measured indirectly using a [3H]-cGMP-radioimmunoassay. All experiments were performed using cultured endothelial cells derived from human umbilical cord veins. Results.The BKCa opener NS1619 (10 µmol/l) significantly increased the BKCa open-state probability (NPo) from 0.011±0.007 (control) to 0.052±0.019. Co-perfusion with nicotine (1 µmol/l) significantly decreased NS1619 induced NPo (n = 14, p < 0.05). Intracellular cGMP levels were significantly increased, if cells w...