Lacasse-M S, Kingma I, Larivière R, Grose J H, Lebel M
Department of Nephrology and Reseach Centre, L'Hôtel-Dieu de Québec Hospital, P.Q., Canada.
Clin Exp Hypertens. 1997 May;19(4):389-401. doi: 10.3109/10641969709084503.
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 < 0.01) 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 < 0.01). 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.
为研究尿毒症在重组人促红细胞生成素(r-HuEPO)所致高血压发生发展中的作用,将Wistar大鼠分为尿毒症组(次全肾切除术)和对照组。三周后,两组再次分组,各亚组分别接受r-HuEPO(100 u/kg皮下注射,每周3次)或溶媒,持续3周。在手术前、接受溶媒或r-HuEPO治疗前以及安乐死之前,测定血细胞比容、血压和血液生化指标。尿毒症组出现了贫血、高血压以及所有在人类终末期肾病中观察到的生化特征。r-HuEPO治疗使尿毒症大鼠的血细胞比容从29±2.5%增至46±2%(p<0.01)。平均基线血压为119±10 mmHg。在第3周时,对照组大鼠的平均血压无变化,但肾切除组的平均血压升至151±5 mmHg(p<0.01)。在第6周时,未接受治疗的尿毒症大鼠的平均血压与第3周相比无变化,但接受r-HuEPO治疗的尿毒症动物的血压显著升高至187±8 mmHg(p<0.01)。在接受r-HuEPO治疗的尿毒症组中,血细胞比容与血压之间无显著相关性(r = 0.01,无统计学意义)。尽管对照组大鼠的血细胞比容显著升高,但r-HuEPO对其血压无影响。这些结果表明,慢性肾衰竭大鼠对r-HuEPO的血压反应增强。