Effect of modifying O2 diffusivity and delivery on glomerular and tubular function in hypoxic perfused kidney

Is O(2) diffusivity within renal capillaries rate limiting for O(2) delivery to hypoxic renal tubules? Equations based on diffusion theory and developed here predict that soluble hemoglobin (Hb) increases O(2) diffusivity by a factor of 1 + [442 Hb%/(P(50) + PO(2))], where P(50) is the partial pressure of O(2) at which the Hb is half saturated. To examine the effect of P(50) and Hb concentrations on renal function, we perfused isolated rat kidneys with Hb-P(35) (P(50) = 35 mmHg) and Hb-P(11) (P(50) = 11 mmHg). Venous PO(2) was lower with Hb-P(11) (10 +/- 1 vs 16 +/- 1 mmHg with arterial PO(2) = 35 mmHg and 28 +/- 2 vs. 40 +/- 2 mmHg with arterial PO(2) = 140 mmHg; P < 0.001). Perfusate P(50) did not influence vascular resistance, glomerular filtration rate, O(2) consumption, Na reabsorption, protein excretion, or free water clearance. Percent glucose and phosphate excretion were lower with Hb-P(11) than with Hb-P(35) (P < 0.001). Urine glucose was 0.17 mmol/l with Hb-P(11) and 0.77 mmol/l with Hb-P(35) (P < 0.001). Hb-P(35) (2%) doubled O(2) delivery and lowered glucose and phosphate excretion to the level obtained with 1% Hb-P(11). Thus Hb-P(11) delivered O(2) twice as effectively as Hb-P(35) to high-affinity sodium glucose and phosphate cotransporters in the late proximal tubule (S3 segment). Hb-P(11) may also have shunted O(2) from the outer cortex to the outer medulla and facilitated O(2) diffusion where PO(2) was low. We conclude that diffusivity is a limiting factor in delivery of O(2) to hypoxic tubules.