Shimada N, Saka S, Sekizuka K, Tanaka A, Takahashi Y, Nakamura T, Ebihara I, Koide H
Division of Nephrology and Hypertension, Department of Medicine, Koto Hospital, Tokyo, Japan.
Ren Fail. 2003 Jul;25(4):569-78. doi: 10.1081/jdi-120022548.
Regular administration of recombinant human erythropoietin (rHuEPO) is frequently associated with a rise in arterial blood pressure in hemodialysis (HD) patients. The aim of this study was to examine the effects of rHuEPO on plasma endothelin (ET)-1 and nitric oxide products (NOx) concentration in HD patients. Fifteen patients on maintenance HD with hematocrit of less than 25% were included in the present study. All patients received 3,000 units of rHuEPO intravenously three times a week at the end of each HD session. Plasma levels of ET-1, NOx, thromboxane B2 (TXB2), prostacyclin (6-keto-PGF1alpha), and cyclic guanosine 3',5'-monophosphate (cGMP) were measured before, 2, and 4 weeks after rHuEPO treatment. Plasma concentrations of ET-1, TXB2, and 6-keto-PGF1alpha were measured by radioimmunoassay. Plasma NOx was measured by high-performance liquid chromatography. An rHuEPO-induced increase in mean arterial blood pressure of over 6 mmHg occurred in 7 patients (hypertensive group), whereas the elevation of mean arterial blood pressure was less than 5 mmHg in 8 patients (nonhypertensive group). Plasma ET-1 levels were elevated in all HD patients. Elevated plasma ET-1 levels remained unchanged after rHuEPO treatment in the hypertensive group, whereas the increase in plasma ET-1 levels was attenuated in the nonhypertensive group. Plasma NOx concentrations were also increased in all HD patients. This increase in plasma NOx levels was lessened in the hypertensive group after rHuEPO administration; however, plasma NOx levels remained increased in the nonhypertensive group. Changes in mean arterial blood pressure were significantly correlated with changes in plasma ET-1/NOx ratio. Plasma levels of TXB2, 6-keto-PGF1alpha, and cGMP were unchanged after rHuEPO administration in the hypertensive and nonhypertensive groups. These results suggest that an increase in ET-1/NOx ratio in blood, probably occurring in vascular endothelial cells, may be associated with rHuEPO-induced hypertension in HD patients.
在血液透析（HD）患者中，定期注射重组人促红细胞生成素（rHuEPO）常常会导致动脉血压升高。本研究旨在探讨rHuEPO对HD患者血浆内皮素（ET）-1和一氧化氮产物（NOx）浓度的影响。本研究纳入了15名维持性HD患者，其血细胞比容低于25%。所有患者在每次HD治疗结束时，每周静脉注射3000单位rHuEPO，共三次。在rHuEPO治疗前、治疗后2周和4周测量血浆ET-1、NOx、血栓素B2（TXB2）、前列环素（6-酮-前列腺素F1α）和环磷酸鸟苷（cGMP）水平。采用放射免疫分析法测定血浆ET-1、TXB2和6-酮-前列腺素F1α浓度。采用高效液相色谱法测定血浆NOx。7例患者（高血压组）rHuEPO诱导平均动脉血压升高超过6 mmHg，而8例患者（非高血压组）平均动脉血压升高小于5 mmHg。所有HD患者血浆ET-1水平均升高。高血压组rHuEPO治疗后血浆ET-1水平升高且保持不变，而非高血压组血浆ET-1水平升高幅度减弱。所有HD患者血浆NOx浓度也升高。rHuEPO给药后，高血压组血浆NOx水平升高幅度减小；然而，非高血压组血浆NOx水平仍升高。平均动脉血压变化与血浆ET-1/NOx比值变化显著相关。高血压组和非高血压组rHuEPO给药后，血浆TXB2、6-酮-前列腺素F1α和cGMP水平均无变化。这些结果表明，血液中ET-1/NOx比值升高可能发生在血管内皮细胞中，这可能与HD患者rHuEPO诱导的高血压有关。
