DIRECT EVIDENCE FOR ERYTHROPOIETIN-INDUCED RELEASE OF ENDOTHELIN FROMPERIPHERAL VASCULAR TISSUE

The effect of recombinant human erythropoietin (r-HuEPO, 0.1 to 2.0 U/ ml) on endothelin-1 (ET-1) release was examined in isolated hind legs perfused with Krebs-Ringer solution from normal rats. r-HuEPO increase d immunoreactive (ir-) ET-1 release in a dose-dependent fasion; the ma ximal percent increment in ir-ET-1 release evoked by r-HuEPO (2.0 U/ml ) was about +210% over the basal rate of release. However, r-HuEPO sho wed no effect on release of angiotensin II, thromboxane B-2 or vasodil atory prostaglandin I-2 from the vasculature. These results not only p rovide direct evidence that r-HuEPO has the potential to specifically stimulate release of ET-1 from peripheral vascular beds, but, hence, s uggest a contributory role of ET-1 in r-HuEPO-induced hypertension in anemic human subjects undergoing r-HuEPO therapy.