O₂-supply to the kidneys and the production of erythropoietin

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 P_O2. 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 P_O2 of renal venous blood descreased 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 (simulated 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 P_O2 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 P_O2 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.