Oxygen sensing in the kidney and its relation to erythropoietin production.

More than 30 years ago the kidney in adult mammals was found to be an essential component of a regulatory feedback loop that controls the number of red blood cells and thereby the oxygen capacity of the blood. The kidney releases a hormone, erythropoietin, that stimulates erythrocyte formation in the bone marrow (26). The rate of release of erythropoietin from the kidney is greatly enhanced by various forms of hypoxia, such as hypoxic hypoxia, anemia, and carbon monoxide poisoning (27). The question that arises, therefore, is whether the oxygen sensor that controls the production of erythropoietin resides outside or inside the kidney. Results of experiments obtained on animals without functioning arterial ehemoreceptors as well as with artificially perfused kidneys or renal hypoperfusion point toward an intrarenal localization of the oxygen sensor (9, 27, 50). In this context, the renal oxygen sensor is operationally defined as a receptor mechanism that controls the production of erythropoietin. This overview aims to conceptualize present knowledge on the physiolog­ ical parameters relevant for the transduction mechanism in the kidney through which the synthesis of erythropoietin might be stimulated. More specifically we discuss (a) the type of oxygen signal that regulates erythropoietin produc­ tion, (b) the location of the oxygen sensor within the kidney, and (c) the transduction mechanism that generates effector molecules that might stimu­ late the synthesis of erythropoietin.