Elevated plasma endothelin concentrations in cyclosporine-treated patients after bone marrow transplantation

Administration of cyclosporine is often associated with the development of renal dysfunction and hypertension. Since recent data from animal experiments provide evidence that endothelin, a potent vasoconstrictive peptide, might play a role in mediating cyclosporine-related renal and cardiovascular side-effects, the present study was designed to investigate whether plasma endothelin concentrations are elevated in cyclosporine-treated patients. Plasma endothelin concentrations, determined by radioimmunoassay after Sep Pak C18 extraction, were significantly elevated in cyclosporine-treated patients after bone marrow transplantation (8.3 +/- 1.4 ng/l, n = 28) compared to patients not treated with cyclosporine after bone marrow transplantation (3.9 +/- 0.2* ng/l, n - 11), patients with haematological disorders (3.9 +/- 0.3** ng/l, n = 11) not treated with bone marrow transplantation and to normal control subjects (3.1 +/- 0.2*** ng/l, n = 33) (*P < 0.05, **P < 0.01, ***P < 0.001). Furthermore, plasma endothelin levels exhibited a significant correlation with cyclosporine concentrations (r = 0.57, P < 0.01). The present data, demonstrating elevated plasma endothelin concentrations in cyclosporine-treated patients, suggest that the cyclosporine-associated renal and cardiovascular side-effects might in part be mediated by cyclosporine-induced stimulation of endothelin release.