RECOMBINANT ERYTHROPOIETIN INCREASES BLOOD-PRESSURE IN EXPERIMENTAL-HYPERTENSION AND UREMIA WITHOUT CHANGE IN VASCULAR CYTOSOLIC CALCIUM

The mechanism of erythropoietin-induced hypertension in dialysis patie nts is unclear. Intracellular calcium ([Ca2+](i)) may be altered in bo th hypertension and uraemia, and the effects of both uraemia and r-HuE PO on vascular smooth muscle [Ca2+](i) and blood pressure (BP) in Wist ar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were therefor e studied. Male WKY and SHR underwent partial nephrectomy or sham oper ation. Three weeks later a 28-day period of treatment with either r-Hu EPO 100 U/kg, s.c., 3 times/week or buffer was commenced (n = 10-12 fo r each subgroup). BP was measured weekly, by noninvasive Doppler tail- cuff assessment. [Ca2+](i) was measured following loading with fura-2 in pooled, primary aortic vascular smooth muscle cells (VSMC). Serum u rea and creatinine rose 3- to 4-fold after partial nephrectomy. Treatm ent with r-HuEPO did not change renal function further in either uraem ic or control WKY or SHR. Haemoglobin increased in both nonuraemic WKY (16.2-20.3 g/dl) and SHR (16.4-20.5 g/dl) and uraemic animals (WKY 13 .9-20.9; SHR 13.8-18.8 g/dl; p < 0.01 for all changes) following 4 wee ks of r-HuEPO treatment. BP was unaffected by r-HuEPO in WKY but incre ased in nonuraemic SHR (210-250; p < 0.01) and in uraemic SHR (224-251 mm Hg; p < 0.001) at 4 weeks. VSMC [Ca2+](i) was higher in SHR than W KY (121 vs, 83 nmol/l; MANOVA p < 0.05) but no effect of uraemia or r- HuEPO on [Ca2+](i) was detected. In conclusion, the hypertensive effec ts of r-HuEPO are augmented both in a genetic model of hypertension an d in uraemia, Although VSMC [Ca2+](i) was elevated in SHR, the further increase in BP induced by r-HuEPO was not associated with alterations in VSMC cytosolic calcium.