The endothelin receptor antagonist, L-754,142 does not prevent cyclosporine A-induced osteopenia in rats

Calcified Tissue International
B R SodamS Epstein

Abstract

Cyclosporine A (CsA) is a potent immunosuppressive agent widely used to prevent allograft rejection. In vivo administration of CsA is associated with the development of high-turnover osteopenia. Endothelin-1 (ET), a vasoconstrictive peptide, has been implicated in CsA-induced nephrotoxicity and hypertension. Recent evidence suggests that endothelin plays a pivotal role in bone metabolism. The present study was designed to investigate whether L-754,142 (ETRA), the combined endothelin A and B receptor antagonist, when given to rats, would favorably modify the bone loss caused by CsA. Fifty, 5-month-old male Sprague-Dawley rats were randomly divided into five groups of 10 rats each. The first group served as a basal control. The remaining four groups received, by daily gavage for 28 days, (1) a combined CsA and ETRA vehicle, (2) CsA, 10 mg/kg, (3) ETRA, 30 mg/kg, and (4) CsA, 10 mg/kg and ETRA, 30 mg/kg, respectively. Rats were weighed and venous blood was collected on days 0, 14, 28 for determination of BUN, creatinine, calcium, PTH, osteocalcin, and 1,25(OH)2 D. Tibiae, after double labeling, were removed following sacrifice for histomorphometry. Both CsA-treated rats and CsA/ETRA-treated rats demonstrated trabecular osteopenia ...Continue Reading

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Citations

Jul 5, 2006·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Jun FujishiroEiji Kobayashi
Mar 12, 2004·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Keisuke IkedaShinya Kawai
Apr 21, 2004·Perception & Psychophysics·S Alex Marinov

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