PLASMA AND BLOOD-VESSEL ENDOTHELIN-1 CONCENTRATIONS IN HYPERTENSIVE UREMIC RATS TREATED WITH ERYTHROPOIETIN

The present study was designed to evaluate whether changes in plasma a nd blood vessel endothelin-1 (ET-1) concentrations may play a role in the enhanced blood pressure response to recombinant human erythropoiet in (r-HuEPO) replacement therapy in uremia. Renal failure was induced by 5/6 nephrectomy (Nx). Uremic rats received either r-HuEPO (100 u s. c. three times a week) or the vehicle for 5 weeks. They were compared to control rats receiving the vehicle. Systolic blood pressure (tail c uff method) hematocrit, serum creatinine, plasma and tissue ET-1 were measured at the end of the protocol. Immunoreactive ET-1 (ir-ET-1) was determined by radioimmunoassay of acid-extracts from the plasma, thor acic aorta and mesenteric arterial bed. Creatinine increased about thr ee fold in Nx animals. Blood pressure in control rats was 120 +/- 3 mm Hg compared to 161 +/- 6 mmHg in the Nx + vehicle group (p <0.01) and 199 +/- 9 mmHg in the Nx + r-HuEPO group (p <0.01 vs Nx + vehicle). He matocrit in control rats was 41.3 +/- 0.4% vs 32.6 +/- 1.8% in the Nx + vehicle group (p <0.01) and 47.6 +/- 1.5% in the Nx + r-HuEPO group (p <0.01), Plasma ir-ET-1 levels were similar in the Nx + vehicle and Nx + r-HuEPO groups (7.9 +/- 1.0 and 7.8 +/- 0.8 pg/ml), In contrast, thoracic aorta ir-ET-1 content was significantly higher in the Nx + r- HuEPO group than in the Nx + vehicle group (20.3 +/- 2.9 vs 13.4 +/- 1 .9 pg, p <0.05). Similar results were obtained in the mesenteric arter ial bed. There were significant correlations between blood pressure an d ir-ET-1 content in the thoracic aorta (r= 0.45, p<0.05) and in the m esenteric arterial bed (r= 0.41, p<0.05), Vascular ET-1 content but no t plasma levels are increased in uremic rats treated with r-HuEPO sugg esting an increase in blood vessel ET-I production which may play a ro le in the pathogenesis of r-HuEPO-induced hypertension.