ERYTHROPOIETIN IMPROVED ENDOTHELIAL DYSFUNCTION AND INFLAMMATION IN 5/6 NEPHRECTOMIZED RAT AORTA BEYOND HEMATOPOIESIS: PP.13.489

Abstract

Objective: We have reported that a low dose (150 U/kg) of erythropoietin inhibited vascular injury in diabetic rats without hematopoiesis (ESH2009). We investigated the effects erythropoietin against vascular injury in renal failure rats. Design and Methods: We administered rHuEPO (75 U/kg, s.c., every 3 days) to 5/6 nephrectomized rats (5/6Nx), which were treated with 1%NaCl in drinking water, for 10 days. Systolic blood pressure (SBP) was measured by tail-cuff method. Hematocrit, urinary protein excretion, creatinine clearance (CCr), and plasma NOx (NO2- + NO3-) levels were examined, and aorta was excised for the following investigations. Acetylcholine-induced relaxation response was determined. Cryosections were prepared to detect macrophages and osteopontin by immunohistochemistry and to stain with hematoxylin-eosin. Immunoblotting was performed to assay the phospho-Akt, phospho-GSK3β, and eNOS proteins. We also treated 5/6 nephrectomized rats with L-arginine. Results: Erythropoietin had no effect on increased SBP or decreased hematorcit in 5/6Nx. Erythropoietin normalized proteinuria and CCr, and improved endothelium-dependent vasodilatation in 5/6Nx. Adventitial infiltration of macrophages, medial overexpression of osteopontin, and medial hyperplasia in 5/6Nx were inhibited by erythropoietin. Erythropoietin reversed the levels of phospho-Akt, phospho-GSK3β, eNOS protein and plasma NOx, which were reduced in 5/6Nx. We also confirmed that L-arginine treatment, which caused increase in plasma NOx, exhibits similar vasoprotective effects as erythropoietin. Conclusions: Low dose of erythropoietin inhibited vascular injury in renal failure rats beyond hematopoiesis.