Effects of an angiotensin II receptor antagonist and angiotensin-converting enzyme inhibitors on burst forming units-erythroid in chronic hemodialysis patients.
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 x 10(5) 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.


CONCLUSIONS
AT1 receptor blockade can directly inhibit erythropoiesis in vitro.
Naito
Masayo
M
Department of Internal Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan. masayo.3.9@mbf.nifty.com
Kawashima
Akira
A
Akiba
Takashi
T
Takanashi
Minoko
M
Nihei
Hiroshi
H
D000328:Adult; D000704:Analysis of Variance; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000494:pharmacology*; D016022:Case-Control Studies; D015773:Enalaprilat / Q000009:adverse effects / Q000494:pharmacology*; D015672:Erythroid Precursor Cells / Q000187:drug effects*; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000627:therapeutic use*; D006400:Hematocrit; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000494:pharmacology*; D019808:Losartan / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007211:Indoles; D004921:Erythropoietin; D015773:Enalaprilat; D019808:Losartan; C061095:trandolaprilat