Vaziri N D, Wang Z Q
Department of Medicine, University of California, Irvine, USA.
Kidney Int. 1996 May;49(5):1457-63. doi: 10.1038/ki.1996.205.
Regular administration of recombinant erythropoietin (EPO) is frequently complicated by a rise in arterial blood pressure. We therefore asked if prolonged stimulation of endogenous EPO production has the same effect. To this end, male Sprague-Dawley rats were placed in a hypobaric chamber (390 mm Hg) for 24 days. The control (NL) group was placed in the chamber at normobaric condition. The animals were then removed from the chamber and monitored through day 108. Plasma EPO peaked within 24 hours and returned to baseline by day 7 and remained so thereafter. Hematocrit rose steadily during the hypoxic phase and declined steadily during the normobaric phase, reaching the baseline on day 45. This was accompanied by parallel changes in erythrocyte mass and blood volume. The rise in hematocrit during hypoxia was accompanied by a parallel rise in blood pressure which peaked on day 24. Despite the restoration of normal hematocrit, erythrocyte mass and blood volume following resumption of normoxia, blood pressure remained elevated throughout the observation period. To dissect the role of hypoxia from that of the associated rise in hematocrit, the experiments were repeated using a group of rats whose hematocrits were kept constant by repeated phlebotomies. These animals exhibited a sustained rise in blood pressure identical to that found in the original group. Thus, prolonged hypobaric hypoxia leads to a severe hematocrit-independent systemic hypertension (HTN) that persists long after the restoration of normoxia. Given the transient nature of the rise in its plasma concentration, endogenous EPO does not appear to play a role in the genesis of the observed systemic HTN. The authors believe that this animal model can be used for future studies of the mechanism, consequences and treatment of acquired HTN.
经常注射重组促红细胞生成素（EPO）常常会因动脉血压升高而变得复杂。因此，我们探讨了内源性EPO生成的长期刺激是否有同样的效果。为此，将雄性Sprague-Dawley大鼠置于低压舱（390毫米汞柱）中24天。对照组（NL）在常压条件下置于舱内。然后将动物从舱中取出并监测至第108天。血浆EPO在24小时内达到峰值，并在第7天恢复到基线水平，此后一直保持。血细胞比容在缺氧阶段稳步上升，在常压阶段稳步下降，在第45天达到基线。这伴随着红细胞量和血容量的平行变化。缺氧期间血细胞比容的升高伴随着血压的平行升高，在第24天达到峰值。尽管恢复常氧后血细胞比容、红细胞量和血容量恢复正常，但在整个观察期内血压仍保持升高。为了区分缺氧与相关血细胞比容升高的作用，使用一组通过反复放血使血细胞比容保持恒定的大鼠重复实验。这些动物的血压持续升高，与原组相同。因此，长期低压缺氧会导致严重的与血细胞比容无关的全身性高血压（HTN），在恢复常氧后仍会持续很长时间。鉴于其血浆浓度升高的短暂性，内源性EPO似乎在观察到的全身性HTN的发生中不起作用。作者认为，这种动物模型可用于未来对获得性HTN的机制、后果和治疗的研究。
