Eckardt K U, Dittmer J, Neumann R, Bauer C, Kurtz A
Department of Physiology, University of Zurich, Switzerland.
Am J Physiol. 1990 May;258(5 Pt 2):F1432-7. doi: 10.1152/ajprenal.1990.258.5.F1432.
Serum erythropoietin (EPO) levels in response to hypoxia are known to decline before an increase in blood oxygen carrying capacity. To define the possible mechanisms underlying this phenomenon, we have investigated 1) how renal EPO mRNA content and EPO production rate underlying the early kinetics of serum EPO levels change under different degrees of normobaric hypoxia, and 2) if a feedback inhibition of either EPO formation or EPO survival in the circulation exists by the hormone itself. We found that serum immunoreactive EPO levels in rats peaked after 12-h exposure to 7.5 or 9% oxygen (2,949 +/- 600 and 756 +/- 108 mU/ml, respectively, mean +/- SE) and declined to 29 and 64% of peak levels, respectively, after 36 h of hypoxia. EPO levels in response to 11.5% oxygen showed no consistent change between 12 (122 +/- 21 mU/ml, mean +/- SE) and 36 h (182 +/- 35 mU/ml) of hypoxia. The decline in EPO levels under severe hypoxia (7.5% O2) was paralleled by a marked reduction in renal EPO mRNA content, indicating that it was primarily a result of diminished hormone production. The observed reductions in serum EPO after 36 h corresponded to preceding declines of calculated EPO production rates from 163- to 62-fold (7.5% O2) and 36- to 25-fold (9% O2) basal values. Application of 50 IU recombinant human EPO to rats 12 h, 6 h, or immediately before hypoxic exposure to mimic the early increase in EPO levels did not affect endogenous EPO formation during a subsequent hypoxic exposure of 12 h.(ABSTRACT TRUNCATED AT 250 WORDS)
已知在血液携氧能力增加之前，血清促红细胞生成素（EPO）水平对低氧的反应会下降。为了确定这一现象背后的可能机制，我们研究了：1）在不同程度的常压低氧条件下，血清EPO水平早期动力学背后的肾脏EPO mRNA含量和EPO产生率如何变化；2）激素本身是否对EPO的形成或在循环中的存活存在反馈抑制。我们发现，大鼠暴露于7.5%或9%氧气12小时后，血清免疫反应性EPO水平达到峰值（分别为2949±600和756±108 mU/ml，平均值±标准误），低氧36小时后分别降至峰值水平的29%和64%。暴露于11.5%氧气时，EPO水平在低氧12小时（122±21 mU/ml，平均值±标准误）和36小时（182±35 mU/ml）之间没有一致变化。严重低氧（7.5% O2）条件下EPO水平的下降与肾脏EPO mRNA含量的显著降低平行，表明这主要是激素产生减少的结果。36小时后观察到的血清EPO降低与之前计算的EPO产生率从基础值的163倍降至62倍（7.5% O2）以及从36倍降至25倍（9% O2）相对应。在低氧暴露前12小时、6小时或立即给大鼠注射50 IU重组人EPO以模拟EPO水平的早期升高，在随后12小时的低氧暴露期间并不影响内源性EPO的形成。（摘要截短于250字）
