AJP - Regulatory, Integrative and Comparative Physiology, Vol 270, Issue 4 744-R748, Copyright © 1996 by American Physiological Society
Endothelin-mediated effect of erythropoietin on blood pressure and renal hemodynamics in hypertensive rats
A. Tojo, M. Doumoto, K. Oka, A. Numabe, K. Kimura and S. Yagi
Department of Medicine, Dokkyo University School of Medicine, Tochigi, Japan.
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), aged 9-12 wk, 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 (1,000
U/kg body wt). In another group of SHR, BQ-123 was continuously infused
(1.2 mg.kg body wt-1.h-1) 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 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 +/- 0.16 to 1.49
+/- 0.18 ml.min-1.100 g body wt-1, 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 +/-
0.26 to 1.88 +/- 0.28 ml.min-1.100 g wt-1, NS). EPO caused a significant
increase in plasma endothelin ET-1 in SHR (from 2.3 +/- 0.6 to 6.3 +/- 1.6
pg/ml, P < 0.05), but not in WKY. In conclusion, 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.
