Atrial natriuretic peptide (ANP) was shown to possess anti-inflammatory potential due to its potency to inhibit the production of inflammatory mediators, such as TNF-alpha. The aim of this study was to determine potential effects of ANP on endothelial cells targeted by TNF-alpha. HUVEC were treated with TNF-alpha and expression of adhesion molecules was investigated by FACS and RT-PCR. Pre-treatment of cells with ANP (30min) significantly reduced TNF-alpha-induced cell surface protein and mRNA expression of E-selectin and ICAM-1, whereas it did not influence VCAM-1. ANP reduced TNF-alpha-induced NF-kappaB activity, which was paralleled by a decreased translocation of p65 to nuclei. ANP did not alter TNF-alpha-induced phosphorylation and degradation of IkappaB-alpha, but attenuated degradation of IkappaB-epsilon. Moreover, ANP leads to a transcriptional induction of IkappaB-alpha. The induction of IkappaB by ANP is suggested as a novel mechanism for regulating inflammatory signalling in endothelial cells, leading to reduced TNF-alpha-induced expression of adhesion molecules.