Renal Oxygenation and Function of the Rat Kidney: Effects of Inspired Oxygen and Preglomerular Oxygen Shunting
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.
KeywordsKidney Oxygenation Shunting
CSW and WJW were supported by grants from the NIH (DK-36079; DK-49870; HL-68686) and from funds from the George E. Schreiner Chair of Nephrology.