Respiration Physiology, 77 (1989) 111-118 Elsevier RESP 01546 111 O2-supply to the kidneys and the production of erythropoietin Horst Pagel, Wolfgang Jelkmann and Christoph Weiss Department of Physiology, Medical University, L~beck, F.R.G. (Accepted for publication 18 February 1989) Abstract. The concentration oferythropoietin (Ep) in blood increases little following a reduction ofthe renal blood flow (rbf). In the present study we examined whether a reduction of rbf in rats induces a lowering of the renal venous Po,. 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 (simulated altitude of 6000 m for 18-20 h) was 431 + 68 mU/ml, when rbfwas 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 02 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 02 sensitive mechanisms. For example, the hypothalamic- hypophyseal system is thought to influence the production of Ep. Erythropoiesis; Erythropoietin; Hypoxia; Kidney; Oxygen partial pressure; Rat; Renal artery stenosis In adult mammals the glycoprotein hormone erythropoietin is derived mainly from peritubular cells in the cortex of the kidney (Koury et al., 1988; Lacombe et al., 1988). It is generally assumed that the production of erythropoietin is determined by the ratio of oxygen supply to oxygen demand of the renal tissue. According to this concept, a lowered oxygen supply to the kidney is accompanied by a rise in the ery~ropoietin level in blood (for summary, see Jelkmann, 1986). However, this hypothesis seems to be at least questionable. Inconsistent data have been reported of erythropoietin production at reduced blood and, thus, at reduced oxygen supply to the kidney. In sporadic clinical studies (Bourgoignie et al., 1968; Taneichi et al., 1986) as well as in studies on laboratory animals (Cooper and Nocenti, 1961; Fisher and Samuels, 1967), an increase of the erythropoietin plasma level was Correspondence address: Dr. H. Pagel, Institut fllr Physiologie, Medizinische Universitat zu Lflbeck, Ratzeburger Allee 160, D-2400 L(ibeck 1, F.R.G. 0034-5687/89/$03.50 © 1989 Elsevier Science Publishers B.V. (Biomedical Division)