Renal Oxygenation and Function of the Rat Kidney: Effects of Inspired Oxygen and Preglomerular Oxygen Shunting

Abstract

We investigated the hypothesis that a preglomerular diffusional shunt for O₂ stabilized renal PO₂ and that changes in intrarenal PO₂ determined nephron nitric oxide (NO) availability for blunting of the tubuloglomerular feedback (TGF) response. The inspired O₂ content of anesthetized rats was changed from normal (21%) to low (10%) or high (100%) for 30–45 min. Direct recordings of PO₂ in the lumens of proximal and distal tubules demonstrated significantly (P < 0.05) lower values at all sites in spontaneously hypertensive rats compared to normotensive Wistar Kyoto (WKY) rats. Low inspired O₂ did not change intratubular PO₂, but high inspired O₂ increased PO₂ modestly (25–50%; P < 0.01) in both strains and at both sites. Addition of 7-nitroindazole (7-NI; 10⁻⁴ M) to artificial tubular fluid perfusing the loop of Henle of WKY nephrons to block neuronal (type 1) nitric oxide synthase in the macula densa increased TGF but this increase was less (P < 0.01) in nephrons of rats breathing high vs. normal inspired O₂ (1.8 ± 0.4 vs. 3.4 ± 0.3 mmHg; P < 0.01). In conclusion, the PO₂ in the renal tubules was effectively buffered from even extreme changes in arterial PO₂, consistent with a functionally important preglomerular O₂ diffusional shunt. However, high inspired PO₂ increased intratubular PO₂ sufficiently to blunt the effects of NO derived from the macula densa, likely reflecting bioinactivation of NO by reactive oxygen species generated at increased PO₂ levels. Thus, the preglomerular diffusional shunt appeared to stabilize intrarenal PO₂ during changes in arterial oxygen and to protect NO signaling within the kidney.