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.
Jilma
B
B
Department of Clinical Pharmacology-TARGET, Vienna University Hospital School of Medicine, Austria.
Szalay
T
T
Dirnberger
E
E
Eichler
H G
HG
Stohlawetz
P
P
Schwarzinger
I
I
Kapiotis
S
S
Wagner
O F
OF
D000328:Adult; D018845:CD11 Antigens / Q000032:analysis; D018821:CD18 Antigens / Q000032:analysis; D015815:Cell Adhesion Molecules / Q000097:blood*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D019332:Endothelin-1 / Q000097:blood / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008297:Male; D010865:Pilot Projects; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D018845:CD11 Antigens; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D019332:Endothelin-1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1