Is tubuloglomerular feedback a tool to prevent nephron oxygen deficiency?

The purpose of the study was to analyze whether rhythmic oscillations of proximal tubular pressure and distal fluid conductivity at the renal surface are induced by oxygen deficiency of thick ascending limb (TAL) segments. Oxygen pressure was measured in halothane anesthetized Munich-Wistar rats by a multi-wire micro-gold electrode at the kidney surface. Signals from wires placed upon glomeruli and tubuli exhibited pO2 oscillations with exactly the same frequency (in mean 30 mHz) as have been described for proximal tubular pressures or distal fluid conductivities. This supports our suggestion that a limited oxygen supply to the nephron forces TAL segments to oscillate between aerobic and anaerobic energy production. A switch to glycolysis reduces TAL's transport efficiency dramatically. At the macula densa, the terminal end of the TAL segment, the thereby elevated sodium concentration operates as a switch by means of the TGF to adapt the filtered load to the oxygen supply of the individual nephron. In this way proximal tubules may also be protected from oxygen deficiency, which is essential due to their low glycolytic capacity. An enhanced halothane concentration of 2% or the use of barbiturates, such as Inactin, blocks oscillations completely as furosemide blocks oscillations as well as the feedback response. Reduction of the hematocrit by exchange transfusion mainly reduces supratubular pO2 values, and to a lesser extent also reduces supraglomerular pressures. This demonstrates that oxygen shunt diffusion in the kidney cortex and medulla is a prerequisite for both the function of a sensor to measure pO2 and oxygen capacity to regulate erythropoietin secretion and to enable an effective adjustment of blood flow to the metabolic and functional demands of the kidney.