Is the renal production of erythropoietin controlled by the brain stem?
Although the structure and function of erythropoietin (Epo) are well documented, the mechanisms of the regulation of the renal synthesis of Epo are still poorly understood. Especially, the description of the localization and function of the O(2)-sensitive sensor regulating the renal synthesis of Epo is insufficient. A body of evidence suggests that extrarenal O(2)-sensitive sensors, localized particularly in the brain stem, play an important role in this connection. To support this concept, high cerebral pressure with consecutive hypoxia of the brain stem was generated by insufflation of synthetic cerebrospinal fluid into the catheterized cisterna magna of rats. When the cerebral pressure of the rats was above the level of their mean arterial blood pressure or the high cerebral pressure persisted for a longer period (>/=10 min), the Epo plasma concentration increased significantly. Bilateral nephrectomy or hypophysectomy before initiation of high intracranial pressure abolished this effect. Systemic parameters (heart rate, blood pressure, Pa(O(2)), Pa(CO(2)), arterial pH, renal blood flow, glucose concentration in blood) were not affected. Other stressors, like restricting the mobility of the rats, had no effect on Epo production. Hence, the effect of high cerebral pressure on renal synthesis of Epo seems to be specific. Increasing cerebral hydrostatic pressure leads to increased renal synthesis of Epo. Obviously, during hypoxia, cerebral O(2)-sensitive sensors release humoral factors, triggering the renal synthesis of Epo. The structure and function of these "Epo-releasing-factors" will have to be characterized in future experiments.
von Wussow
Ursula
U
Institut für Physiologie, Universität zu Lübeck, Ratzeburger Allee 160, D-23538 Lubeck, Germany.
Klaus
Janina
J
Pagel
Horst
H
D000818:Animals; D001933:Brain Stem / Q000503:physiopathology*; D004921:Erythropoietin / Q000378:metabolism*; D006706:Homeostasis; D007016:Hypophysectomy; D000860:Hypoxia / Q000378:metabolism*; D007427:Intracranial Pressure; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004921:Erythropoietin; D010100:Oxygen