Background: Angiotensin-converting enzyme (ACE) inhibitors have been reported to reduce the response to erythropoietin (EPO) administration in chronic hemodialysis patients, but the mechanism for this effect has not yet been clarified. To clarify the mechanism of ACE inhibitors- and angiotensin II type 1 (AT1) receptor antagonist-induced anemia in hemodialysis patients, we examined the effect of ACE inhibitors and AT1 receptor antagonist on burst-forming units-erythroid (BFU-E) in the peripheral blood of hemodialysis patients and healthy controls in vitro. Methods: Peripheral blood mononuclear cells (PBMNCs) were isolated by gradient centrifugation from 10 patients on regular hemodialysis and 7 healthy control volunteers. A colony assay of hematopoietic progenitors was performed using the methylcellulose culture system. PBMNCs of 1 or 2 × 105 were plated in a medium containing EPO with various concentrations of ACE inhibitors or AT1 receptor antagonist and incubated for 14 days. Colonies of BFU-E were counted under an inverted microscope. Results: The PBMNCs from the chronic hemodialysis patients formed fewer BFU-Es than those from healthy volunteers. AT1 receptor antagonist in both healthy volunteers and hemodialysis patients suppressed the number of BFU-Es. The ACE inhibitors produced a smaller effect than the AT1 receptor antagonist. Conclusion: AT1 receptor blockade can directly inhibit erythropoiesis in vitro.
We believe that this procedure for isolating kidney lysosome will be useful in the study of the mechanisms of specific modification, processing and catabolism of proteins.
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