Prevention of erythropoietin-associated hypertension.
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.
Lee
Mary S
MS
School of Medicine, Northwestern University, Chicago, IL, USA.
Lee
John S
JS
Lee
Jong Y
JY
D000818:Animals; D001795:Blood Pressure Determination; D001835:Body Weight; D002940:Circadian Rhythm; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D000068817:Epoetin Alfa; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000008:administration & dosage* / Q000009:adverse effects*; D006400:Hematocrit; D006973:Hypertension / Q000139:chemically induced* / Q000517:prevention & control*; D011336:Probability; D011485:Protein Binding; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D012016:Reference Values; D012307:Risk Factors; D012680:Sensitivity and Specificity
D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa