Lee Mary S, Lee John S, Lee Jong Y
School of Medicine, Northwestern University, Chicago, IL, USA.
Hypertension. 2007 Aug;50(2):439-45. doi: 10.1161/HYPERTENSIONAHA.107.090423. Epub 2007 Jun 4.
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.
高血压是促红细胞生成素（Epo）治疗最显著的并发症。Epo诱导的高血压能否消除？我们在午夜、凌晨4点、上午8点、中午、下午4点和晚上8点，对随机分组的斯普拉格-道利大鼠，研究了我们的基因工程产品促红细胞生成素结合蛋白（Epo-bp）和抗Epo-bp抗体的全身和局部作用。在为期4周、每周两次注射Epo（50 U/kg）、Epo-bp、抗Epo-bp抗体或生理盐水的疗程开始前和结束后，立即测量血压、血细胞比容和体重。与生理盐水、Epo-bp和抗Epo-bp抗体组相比，Epo治疗总体上显著提高了血细胞比容（分别为0.616对0.427、0.439和0.441），并且在6个测试时间点均如此（所有P<0.0001）。Epo联合Epo-bp和抗Epo-bp抗体治疗对Epo诱导的血细胞比容增加几乎没有影响（分别为0.616对0.580或0.591）。Epo组与生理盐水、Epo-bp和抗Epo-bp抗体组的昼夜血压分别为136.2±2.3对116.2±1.7、118.4±2.1和116.6±2.1 mmHg（各P<0.0001）。Epo治疗在中午、下午4点、晚上8点和午夜检测到血压显著升高。当Epo与Epo-bp或抗Epo-bp抗体联合使用时，与单独使用Epo治疗相比，血压维持在与生理盐水治疗相似的水平（各P<0.0001）。总体而言，Epo治疗组的身体、大脑和心脏重量显著低于其他组。因此，Epo-bp和抗Epo-bp抗体可消除Epo诱导的高血压，而不影响血细胞比容和血容量。
