EFFECT OF MODIFYING O-2 DIFFUSIVITY AND DELIVERY ON GLOMERULAR AND TUBULAR FUNCTION IN HYPOXIC PERFUSED KIDNEY

Is O-2 diffusivity within renal capillaries rate limiting for O-2 deli very to hypoxic renal tubules? Equations based on diffusion theory and developed here predict that soluble hemoglobin (Hb) increases O-2 dif fusivity by a factor of 1 + [442 Hb%/(P-50 + PO2)], 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 perfuse d isolated rat kidneys with Hb-P-35 (P-50 = 35 mmHg) and Hb-P-11 (P-50 = 11 mmHg). Venous PO2 was lower with Hb-P-11 (10 +/- 1 vs 16 +/- 1 m mHg with arterial PO2 = 35 mmHg and 28 +/- 2 vs. 40 +/- 2 mmHg with ar terial PO2 = 140 mmHg; P < 0.001). Perfusate P-50 did not influence va scular resistance, glomerular filtration rate, O-2 consumption, Na rea bsorption, 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 w ith 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-a ffinity sodium glucose and phosphate cotransporters in the late proxim al tubule (S3 segment). Hb-P-11 may also have shunted O-2 from the out er cortex to the outer medulla and facilitated O-2 diffusion where PO2 was low. We conclude that diffusivity is a limiting factor in deliver y of O-2 to hypoxic tubules.