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Prevention of Erythropoietin-Associated Hypertension
Mary S. Lee; John S. Lee; Jong Y. Lee
From the School of Medicine (M.S.L.), Northwestern University, Chicago, Ill; and the Department of Medicine (J.S.L., J.Y.L.), University of Minnesota School of Medicine, Minneapolis.
Hypertension is the most significant complication from treatment with erythropoietin (Epo). Can Epo-induced hypertension be eliminated? We examined systemic and local effects of our genetically engineered products, Epo-binding protein (Epo-bp) and anti–Epo-bp antibodies, on randomly assigned Sprague–Dawley rats at midnight, 4 AM, 8 AM, noon, 4 PM, and 8 PM. Blood pressure, hematocrit, and body weight were measured immediately before and after the completion of a 4-week, twice-weekly course of Epo (50 U/kg), Epo-bp, anti–Epo-bp antibodies, or physiological saline injections. Epo treatment increased hematocrit markedly overall as compared with the saline, Epo-bp, and anti–Epo-bp antibody groups (0.616 versus 0.427, 0.439, and 0.441, respectively) and at each of the 6 test times (all P<0.0001). Epo-bp and anti–Epo-bp antibody treatment with Epo had almost no effect on the Epo-induced hematocrit increase (0.616 versus 0.580 or 0.591, respectively). Circadian blood pressures for Epo versus saline, Epo-bp, and anti–Epo-bp antibody groups were 136.2±2.3 versus 116.2±1.7, 118.4±2.1, and 116.6±2.1 mm Hg, respectively (each P<0.0001). Significantly increased blood pressure was detected at noon, 4 PM, 8 PM, and midnight in Epo treatment. When Epo was given with Epo-bp or anti–Epo-bp antibodies, blood pressure was maintained at similar levels as in saline treatment (each P<0.0001) as compared with Epo treatment alone. Overall, body, brain, and heart weights were significantly lower in Epo treatment than those of other groups. Thus, Epo-bp and anti–Epo-bp antibodies eliminate Epo-induced hypertension without affecting hematocrit and blood volume.
Key Words: erythropoiesis • erythropoietin-binding protein • circadian effects • hypertension • splenomegaly • cardiovascular parameters
