Nephrology Dialysis Transplantation, Vol 13, Issue 11 2877-2883, Copyright © 1998 by Oxford University Press
D Kang, K Yoon and D Han
Background: The pathogenesis of rHuEpo-induced
hypertension in haemodialysis (HD) patients still remains uncertain.
Endothelin-1 (ET-1) is produced from proendothelin-1 (proET-1) by an
endothelin-converting enzyme. Since proET-1 is known to have approximately
1/100 the potency of ET-1 for contracting an isolated blood vessel, the
change in the activity of endothelin-converting enzyme (ECE) has been
proposed as an important factor in the pathophysiology of various
hypertensive diseases. However there is no report on whether a change in
the rate of conversion of proET-1 to ET-1 may be involved in the
pathogenesis of rHuEpo-induced hypertension. The purpose of this study was
to ascertain the potential role of ECE in the development of rHuEpo-induced
hypertension. Methods: The levels of plasma
erythropoietin, proET-1, ET-1, and mean arterial blood pressure (MAP) were
measured following a single dose of rHuEpo (100 U/kg) in HD patients with
24-h ambulatory blood pressure monitoring. Different routes of
administration (19 intravenous group, 10 subcutaneous group) were compared
to a placebo-injected control group (10 HD patients).
Results: Plasma erythropoietin levels reached maximal
value 5 min after i.v injection of rHuEpo (13.1±2.4
vs 2780.9±290.1 mU/ml, P<0.01),
whereas it was 6h in the s.c. group (14.7±3.8
vs 38.8±17.7 mU/ml, P<0.05). A
significant increase in MAP was noted 30 min after rHuEpo injection, which
lasted for 3 h in the i.v. group. However, no significant changes in MAP
were noted in patients given rHuEpo subcutaneously. Both the plasma
concentrations of proET-1 and ET-1 started to increase from 10 min after
i.v. rHuEpo administration, with the pro-ET-1 reaching a peak level at 30
min (13.5±7.4 vs 21.6±3.8 pg/ml,
P<0.05) and the ET-1 at 1 h (4.2±2.6
vs 9.9±4.8 pg/ml, P<0.05). In
patients with significant interdialysis hypertension following a single
i.v. injection of rHuEpo, the molar ratio of ET-1 over proET-1
(ET-1/proET-1) was significantly higher than in patients without
hypertension. In addition, the increase in ET-1 levels was significantly
greater in patients with interdialysis hypertension, while changes in
proET-1 level were similar in both hypertensive and non-hypertensive
groups. Changes in interdialysis MAP (Dgr;IDMAP) was significantly
correlated with &Dgr;ET-1 during the interdialysis period, but not with
&Dgr;proET-1. Conclusion: Differences in
ET-1/proET-1 ratio in relation to changes in MAP after a single intravenous
administration of rHuEpo suggest a potential role for ECE in the
pathogenesis of rHuEpo-induced hypertension. Key
words: endothelin-1; endothelin-converting enzyme;
haemodialysis; proendothelin-1; rHuEpo-induced hypertension
ORIGINAL ARTICLES
Acute effects of recombinant human erythropoietin on plasma levels of proendothelin-1 and endothelin-1 in haemodialysis patients
Division of Nephrology, Department of Internal Medicine, Ewha Women's University Hospital, 60 Chongno 6-ga, Chongno-gu, Seoul 110-126, Korea; Yonsei University, Seoul, Korea; Corresponding author
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