The influence of low-density lipoproteins on endothelin receptor B (ET_B) expression in endothelial cells is currently unknown. Therefore, the effect of native and oxidized low-density lipoprotein (nLDL, oxLDL) on the expression of ET_B was studied in primary cultures of human umbilical vein endothelial cells (HUVEC). HUVEC were stimulated by nLDL and oxLDL in a time (1 to 12 h) and dose (25 to 100 mg/ml)-dependent manner. In order to analyze signal transduction pathways involved in the regulation of ET_B, protein kinase C was inhibited using 100 nM Ro-31–8220. The mRNA expression of ET_B was determined by quantitative RT-PCR and ET_B protein expression by Western blot. Native LDL induced ET_B mRNA after 1 h 2fold. Stimulation of HUVEC with oxLDL increased ET_B mRNA expression 3-fold. Native LDL was even more potent than oxLDL inducing ET_B protein expression. Induction of ET_B expression by oxLDL is mediated by PKC. These data demonstrate that low-density lipoproteins even independent of oxidative modification are potent inducers of endothelial ET_B receptors at the mRNA and protein level. Given the NO releasing capacity of endothelial ET_B receptors, this effect may represent a possible vasoprotective mechanism.