ENDOTHELIN-MEDIATED EFFECT OF ERYTHROPOIETIN ON BLOOD-PRESSURE AND RENAL HEMODYNAMICS IN HYPERTENSIVE RATS

Erythropoietin (EPO) has been reported to induce hypertension in hemod ialysis patients with family history of hypertension. In this study, t o reveal the mechanism of EPO-induced hypertension, we examined the ac ute effect of EPO on blood pressure (BP) and renal hemodynamics in gen etically hypertensive rats, and we also tested the effect of BQ-123, a n endothelin ETA-receptor blocker, on EPO-induced changes in hemodynam ics. Male spontaneously hypertensive rats (SHR) and normotensive Wista r-Kyoto rats (WKY), aged 9-12 wk, were anesthetized, and BP was monito red through the carotid artery. Renal plasma dow (RPF) and glomerular filtration rate (GFR) were measured before and after an intravenous in jection of EPO (1000 U/kg body wt). In another group of SHR, BQ-123 wa s continuously infused (1.2 mg . kg body wt(-1). h(-1)) during the exp eriments. The acute injections of EPO increased BP significantly in SH R in a dose-dependent manner, whereas WKY did not show a significant i ncrease 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 si gnificantly (from 1.78 +/- 0.16 to 1.49 +/- 0.18 ml . min(-1). 100g bo dy 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 body wt(-1), NS). EPO caused a significant in crease 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 administrati on of EPO raised blood pressure and reduced RPF in SHR, and these vaso constrictive effects of EPO are mediated via ET(A) receptors by an enh anced ET-1 release.