Pagel H, Jelkmann W, Weiss C
Department of Physiology, Medical University, Lübeck, F.R.G.
Respir Physiol. 1989 Jul;77(1):111-7. doi: 10.1016/0034-5687(89)90034-0.
The concentration of erythropoietin (Ep) in blood increases little following a reduction of the renal blood flow (rbf). In the present study we examined whether a reduction of rbf in rats induces a lowering of the renal venous PO2. In addition, the combined effects of reduced rbf and hypobaric hypoxia on the production of Ep were studied. To lower rbf, silver clips with stepwisely reduced inner diameters were applied on both renal arteries. The PO2 of renal venous blood decreased gradually to values below 10 mm Hg, when rbf was reduced from 80 to 10% of normal. Under these conditions plasma Ep increased only moderately from 20 +/- 6 to 69 +/- 24 mU/ml within 18-20 h. However, plasma Ep of rats exposed to hypobaric hypoxia (stimulated altitude of 6000 m for 18-20 h) was 431 +/- 68 mU/ml, when rbf was 100-80% of normal, compared to 931 +/- 91 mU/ml, when rbf was reduced to 40-10%. Thus, a reduction of the blood flow to the kidney appears to be no major stimulus for the production of Ep, even when the PO2 in the kidney becomes very low. However, plasma levels of Ep increase markedly, when the whole body O2 offer is lowered. These results support the view that Ep production is not only dependent on the PO2 in the kidney but also under the control of extrarenal O2 sensitive mechanisms. For example, the hypothalamic-hypophyseal system is thought to influence the production of Ep.
肾血流量（RBF）减少后，血液中促红细胞生成素（Ep）的浓度几乎没有增加。在本研究中，我们检测了大鼠RBF减少是否会导致肾静脉PO₂降低。此外，还研究了RBF减少和低压缺氧对Ep产生的联合影响。为了降低RBF，在双侧肾动脉上应用内径逐步减小的银夹。当RBF从正常的80%降至10%时，肾静脉血的PO₂逐渐降至10 mmHg以下。在这些条件下，血浆Ep在18 - 20小时内仅适度增加，从20±6 mU/ml增至69±24 mU/ml。然而，当RBF为正常的100 - 80%时，暴露于低压缺氧（模拟海拔6000米，持续18 - 20小时）的大鼠血浆Ep为431±68 mU/ml，而当RBF降至40 - 10%时，血浆Ep为931±91 mU/ml。因此，即使肾脏中的PO₂变得非常低，肾血流量的减少似乎也不是Ep产生的主要刺激因素。然而，当全身氧气供应降低时，血浆Ep水平会显著升高。这些结果支持这样一种观点，即Ep的产生不仅取决于肾脏中的PO₂，还受肾外氧敏感机制的控制。例如，下丘脑 - 垂体系统被认为会影响Ep的产生。
