Role of nitric-oxide resistance in erythropoietin-induced
hypertension in rats with chronic renal failure.
Vaziri, N. D., X. J. Zhou, F. Naqvi, J. Smith, F. Oveisi, Z. Q. Wang,
and R. E. Purdy.
Division of Nephrology, Department of Medicine, University of
California, Irvine, Irvine, California 92717
APStracts 3:0041E, 1996.
We studied the mechanism of erythropoietin (EPO) induced hypertension
(HTN) in rats with chronic renal failure (CRF). After 5/6
nephrectomy, rats were randomized into four groups. Group A received
EPO, 150 U/kg, twice weekly for six weeks to prevent anemia; group B
received placebo injections and became anemic. Group C received EPO
but was kept anemic by dietary iron deficiency. Group D received
placebo and regular transfusions to match hematocrit (Hct) in group
A. Blood pressure (BP), Hct, platelet [Ca++]i and [Mg++]i, and
pressor and vasodilatory responses were determined. By design, Hcts
in groups A and D were comparable and significantly greater (p
<0.01) than in groups B and C. Despite divergent Hct values, the
EPO-treated groups A and C showed a significant rise in BP compared
to the placebo-treated groups B and D. HTN occurred whether EPO
therapy was begun immediately or four weeks after nephrectomy. EPO
therapy augmented the elevation of basal [Ca++]i and restored the
defective thrombin-mediated rise of platelet [Ca++]i in CRF animals.
EPO therapy did not alter caudal artery contraction in response to
either 68 mM K+-induced depolarization, angiotensin II or [alpha]-1
agonist, methoxamine in vitro or the pressor response to angiotensin
II in vivo. However, EPO therapy impaired the hypotensive response to
nitric oxide (NO)-donors, sodium nitroprusside and S-nitroso-N
-acetyl-D,L-penicillamine, and reversed the CRF-induced upregulation
of cGMP production by thoracic aorta in vitro. Thus, EPO-induced HTN
in CRF rats is hematocrit independent and is associated with and
perhaps causally related to increased basal and stimulated [Ca++]i
and impaired vasodilatory response to NO.
Received 31 October 1995; accepted in final form 20 February
1996.
APS Manuscript Number E485-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 March 96