Endothelin-mediated effect of erythropoietin on blood pressure and
renal hemodynamics in spontaneously hypertensive rats.
Tojo, Akihiro, Maho Doumoto, Kazuo Oka, Atsushi Numabe, Kenjiro
Kimura, and Shigeru Yagi.
Department of Medicine, Division of Hypertension and Cardiorenal
Disease, Dokkyo University School of Medicine, Tochigi 321-02, Japan,
The Second Department of Internal Medicine, University of Tokyo,
Bunkyo, Tokyo 113, Japan
APStracts 2:0303R, 1995.
Erythropoietin (EPO) has been reported to induce hypertension in
hemodialysis patients with family history of hypertension. In this
study, to reveal the mechanism of EPO-induced hypertension, we
examined the acute effect of EPO on blood pressure (BP) and renal
hemodynamics in genetically hypertensive rats, and we also tested the
effect of BQ-123, an endothelin ETA receptor blocker, on EPO-induced
changes in hemodynamics. Male spontaneously hypertensive rats (SHR)
and normotensive Wistar-Kyoto rats (WKY) aging 9 to 12 weeks were
anesthetized, and BP was monitored through the carotid artery. Renal
plasma flow (RPF) and glomerular filtration rate (GFR) were measured
before and after an intravenous injection of EPO (1000 U/kg BW). In
another group of SHR, BQ-123 was continuously infused (1.2 mg/kg
BW/hr) during the experiments. The acute injections of EPO increased
BP significantly in SHR in a dose-dependent manner, whereas WKY did
not show a significant increase in BP after the EPO injections. The
effect of EPO on BP in SHR was blocked by BQ-123. In SHR, an acute
injection of EPO decreased RPF significantly (from 1.78 [umlaut]u}
0.16 to 1.49 [umlaut]u} 0.18 ml/min/100g BW, p<0.05) without a
change in GFR, whereas WKY did not show significant changes in either
RPF or GFR. The effect of EPO on RPF in SHR was completely blocked by
BQ-123 (from 1.92 [umlaut]u} 0.26 to 1.88 [umlaut]u} 0.28, NS). EPO
caused a significant increase in plasma endothelin ET-1 in SHR (from
2.3 [umlaut]u} 0.6 to 6.3 [umlaut]u} 1.6 pg/ml, p<0.05), but not
in WKY. In conclusion, the acute administration of EPO raised blood
pressure and reduced RPF in SHR, and these vasoconstrictive effects
of EPO are mediated via ETA receptors by an enhanced ET-1 release.
Received 6 March 1995; accepted in final form 23 October 1995.
APS Manuscript Number R144-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 November 95