von Wussow Ursula, Klaus Janina, Pagel Horst
Institut für Physiologie, Universität zu Lübeck, Ratzeburger Allee 160, D-23538 Lubeck, Germany.
Am J Physiol Endocrinol Metab. 2005 Jul;289(1):E82-6. doi: 10.1152/ajpendo.00182.2004. Epub 2005 Feb 22.
Although the structure and function of erythropoietin (Epo) are well documented, the mechanisms of the regulation of the renal synthesis of Epo are still poorly understood. Especially, the description of the localization and function of the O(2)-sensitive sensor regulating the renal synthesis of Epo is insufficient. A body of evidence suggests that extrarenal O(2)-sensitive sensors, localized particularly in the brain stem, play an important role in this connection. To support this concept, high cerebral pressure with consecutive hypoxia of the brain stem was generated by insufflation of synthetic cerebrospinal fluid into the catheterized cisterna magna of rats. When the cerebral pressure of the rats was above the level of their mean arterial blood pressure or the high cerebral pressure persisted for a longer period (>/=10 min), the Epo plasma concentration increased significantly. Bilateral nephrectomy or hypophysectomy before initiation of high intracranial pressure abolished this effect. Systemic parameters (heart rate, blood pressure, Pa(O(2)), Pa(CO(2)), arterial pH, renal blood flow, glucose concentration in blood) were not affected. Other stressors, like restricting the mobility of the rats, had no effect on Epo production. Hence, the effect of high cerebral pressure on renal synthesis of Epo seems to be specific. Increasing cerebral hydrostatic pressure leads to increased renal synthesis of Epo. Obviously, during hypoxia, cerebral O(2)-sensitive sensors release humoral factors, triggering the renal synthesis of Epo. The structure and function of these "Epo-releasing-factors" will have to be characterized in future experiments.
尽管促红细胞生成素（Epo）的结构和功能已有充分记载，但对其肾脏合成调节机制仍知之甚少。特别是，对调节Epo肾脏合成的氧敏感传感器的定位和功能描述不足。大量证据表明，肾外氧敏感传感器，特别是位于脑干的传感器，在这方面起着重要作用。为支持这一概念，通过向大鼠导管插入的小脑延髓池注入合成脑脊液，制造出高脑压并伴有脑干连续性缺氧。当大鼠脑压高于其平均动脉血压水平或高脑压持续较长时间（≥10分钟）时，血浆促红细胞生成素浓度显著升高。在颅内高压开始前进行双侧肾切除或垂体切除可消除这种效应。全身参数（心率、血压、动脉血氧分压、动脉血二氧化碳分压、动脉pH值、肾血流量、血糖浓度）未受影响。其他应激源，如限制大鼠活动，对促红细胞生成素的产生没有影响。因此，高脑压对Epo肾脏合成的影响似乎具有特异性。增加脑静水压力会导致Epo的肾脏合成增加。显然，在缺氧期间，脑氧敏感传感器释放体液因子，触发Epo的肾脏合成。这些“促红细胞生成素释放因子”的结构和功能将在未来实验中进行表征。
