Uremia Enhances the Blood Pressure Response to Erythropoietin

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Abstract
To investigate the role of uremia in the development of human recombinant erythropoietin (r-HuEPO)-induced hypertension, Wistar rats were divided into a uremic (subtotal nephrectomy) and a control group. After three weeks, both groups were again divided and each subgroup received either r-HuEPO (100 u/kg s.c., 3 times weekly) or the vehicle for a further 3 weeks. Hematocrit, blood pressure and blood chemistry were measured prior to surgery, before either vehicle or r-HuEPO treatment and before euthanasia. The uremic group developed anemia, hypertension and all the biochemical features observed in humans with end-stage renal disease. r-HuEPO therapy increased hematocrit from 29 ± 2.5% to 46 ± 2% (p < 0.01) in the uremic rats. The mean baseline blood pressure was 119 ± 10 mmHg. At week 3, mean blood pressure was unchanged in control rats, but it was increased to 151 & 5 mmHg (p CO.01) in the nephrectomized group. At week 6, mean blood pressure in the untreated uremic rats remained unchanged from week 3, but blood pressure in the uremic animals treated with r-HuEPO increased significantly to 187 & 8 mmHg (p CO.01). There was no significant correlation between hematocrit and blood pressure in the r-HuEPO treated uremic group (r=0.01, NS). r-HuEPO had no effect on blood pressure in control rats despite a significant increase in hematocrit. These results indicate that the blood pressure response to r-HuEPO is enhanced in rats with chronic renal failure.