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Effects of endothelin‐1 on circulating adhesion molecules in man
Author(s) -
JILMA B.,
SZALAY T.,
DIRNBERGER E.,
EICHLER H.G.,
STOHLAWETZ P.,
SCHWARZINGER I.,
KAPIOTIS S.,
WAGNER O. F.
Publication year - 1997
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.1997.2080755.x
Subject(s) - cell adhesion molecule , cd18 , selectin , medicine , adhesion , endocrinology , soluble cell adhesion molecules , endothelin 1 , cell adhesion , chemistry , p selectin , immunology , endothelin receptor , intercellular adhesion molecule 1 , andrology , integrin alpha m , platelet , flow cytometry , platelet activation , receptor , organic chemistry
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.