Effect of modifying O2diffusivity and delivery on glomerular and tubular function in hypoxic perfused kidney.

Is O2 diffusivity within renal capillaries rate limiting for O2 delivery to hypoxic renal tubules? Equations based on diffusion theory and developed here predict that soluble hemoglobin (Hb) increases O2 diffusivity by a factor of 1 + [442 Hb%/(P50 +[Formula: see text])], where P50 is the partial pressure of O2 at which the Hb is half saturated. To examine the effect of P50 and Hb concentrations on renal function, we perfused isolated rat kidneys with Hb-P35(P50 = 35 mmHg) and Hb-P11(P50 = 11 mmHg). Venous[Formula: see text] was lower with Hb-P11 (10 ± 1 vs 16 ± 1 mmHg with arterial [Formula: see text] = 35 mmHg and 28 ± 2 vs. 40 ± 2 mmHg with arterial[Formula: see text] =140 mmHg; P < 0.001). Perfusate P50 did not influence vascular resistance, glomerular filtration rate, O2 consumption, Na reabsorption, protein excretion, or free water clearance. Percent glucose and phosphate excretion were lower with Hb-P11 than with Hb-P35( P < 0.001). Urine glucose was 0.17 mmol/l with Hb-P11 and 0.77 mmol/l with Hb-P35( P < 0.001). Hb-P35 (2%) doubled O2 delivery and lowered glucose and phosphate excretion to the level obtained with 1% Hb-P11. Thus Hb-P11 delivered O2 twice as effectively as Hb-P35 to high-affinity sodium glucose and phosphate cotransporters in the late proximal tubule (S3 segment). Hb-P11 may also have shunted O2 from the outer cortex to the outer medulla and facilitated O2 diffusion where[Formula: see text] was low. We conclude that diffusivity is a limiting factor in delivery of O2 to hypoxic tubules.