Scholz H, Schurek H J, Eckardt K U, Kurtz A, Bauer C
Physiologisches Institut der Universität, Zürich, Switzerland.
Pflugers Arch. 1991 Apr;418(3):228-33. doi: 10.1007/BF00370520.
In this study we have investigated the role of oxygen delivery and of classic second messengers on erythropoietin production by the isolated perfused rat kidney. We found that the rat kidney was capable of de novo synthesis of erythropoietin. The erythropoietin production rate was inversely related to the oxygen pressure in the perfusate and increased from 0.17 to 1.85 U erythropoietin h-1 g kidney-1 when arterial PO2 was lowered from 500 mmHg to 30 mmHg. Addition of forskolin (10 microM) and 8-bromo-cGMP (100 microM) to the perfusate elicited significant effects on the renal vascular resistance, but had no significant effect on erythropoietin production. Hypoxia-induced erythropoietin formation, however, was blocked by calmidazolium (1 microM) and W-7 (10 microM), two structurally different putative calmodulin antagonists. Calmidazolium and W-7 had no effect on other functional parameters of the isolated perfused rat kidney such as flow rate, glomerular filtration rate or sodium reabsorption. Our findings suggest that the oxygen-sensing mechanism that controls renal erythropoietin production is primarily located in the kidney itself. A calcium/calmodulin-dependent cellular reaction could be involved in the signal transduction process.
在本研究中，我们调查了氧输送及经典第二信使对离体灌注大鼠肾脏促红细胞生成素产生的作用。我们发现大鼠肾脏能够从头合成促红细胞生成素。促红细胞生成素的产生速率与灌注液中的氧分压呈负相关，当动脉血氧分压从500 mmHg降至30 mmHg时，促红细胞生成素的产生速率从0.17 U促红细胞生成素·h⁻¹·g肾脏⁻¹增加至1.85 U促红细胞生成素·h⁻¹·g肾脏⁻¹。向灌注液中添加福司可林（10 μM）和8-溴-cGMP（100 μM）对肾血管阻力有显著影响，但对促红细胞生成素的产生无显著影响。然而，钙调蛋白拮抗剂氯米帕明（1 μM）和W-7（10 μM）可阻断低氧诱导的促红细胞生成素形成，这两种拮抗剂结构不同。氯米帕明和W-7对离体灌注大鼠肾脏的其他功能参数如流速、肾小球滤过率或钠重吸收无影响。我们的研究结果表明，控制肾脏促红细胞生成素产生的氧传感机制主要位于肾脏本身。钙/钙调蛋白依赖性细胞反应可能参与信号转导过程。
