Effects of endothelin-1 on circulating adhesion molecules in man

Several studies point to a role for endothelin-1 (ET-1) in enhancing adhesion molecule expression and leucocyte adhesion. We thus hypothesized that ET-1 would induce expression of adhesion molecules by endothelial cells and by leucocytes in humans, and hence compared with placebo the effect of a continuous 6-h ET-1 infusion on plasma levels of circulating (c)E-selectin, cP-selectin, intercellular and vascular cell adhesion molecule 1. In addition, we investigated the effects of ET-1 on expression of the leucocyte adhesion molecules CD11b/CD18 and L-selectin on monocytes and neutrophils. After an open pilot study to evaluate the safety of a 6-h ET-1 infusion of 0.4 pmol kg⁻¹ min⁻¹ ( n  = 4), the main study was conducted as a randomized, double-blind, two-way, cross-over trial in 12 additional young healthy male volunteers, who received the same treatment and were observed over a period of 24 h. ET-1 infusion decreased renal plasma flow by 43% (CI 35–51%; P  < 0.001) and increased the filtration fraction by 80% (CI 20–110%; P  < 0.001). Heart rate decreased by −10% (CI −4% to −15%) at 6 h under ET-1 infusion in the cross-over trial ( P  = 0.012 between periods). Although ET-1 infusions increased plasma levels of ET-1 by about 300%, ET-1 elicited no relevant changes in any circulating adhesion molecules or leucocyte adhesion molecules measured. In the placebo period small diurnal changes were observed for cP-selectin (–8%, CI −14 to −3%, P  = 0.008) and cE-selectin (–6%, CI −10 to −3%, P  = 0.003) at 12 h (20.45 h). In sum, ET-1 does not regulate circulating adhesion molecules in healthy men. Circadian variations may exist for plasma levels of cP-selectin and cE-selectin.