Uric acid excretion by the rat kidney.

The renal excretion of uric acid was studied in nondiuretic (ND) male Wistar rats and in the same animals subsequently made diuretic (D) by the infusion of hypertonic saline. Clearances of endogenous urate and of inulin, determined chemically, were compared with the simultaneous clearance of 14C infused as [6(-14)C]urate or [2(-14)C]urate. In rats infused with [6(-14)C]urate the isotope/inulin clearance ratios were 0.29 +/- 0.09 (ND) and 0.31 +/- 0.11 (D) ml/min; the simultaneous urate (chemical)/inulin ratios were 0.21 +/- 0.07 (ND) and 0.24 +/- 0.08 (D) ml/min. In rats infused with [2(-14)C]urate the isotope/inulin clearance ratios were 1.02 +/- 0.5 (ND) and 1.13 +/- 0.9 ml/min (D); the simultaneous urate (chemical)/inulin clearance ratios were much lower-0.19 +/- 0.09 (ND) and 0.32 +/- 0.19 (D) ml/min. Thin-layer chromatography of urine after [6(-14)C]urate inl uric acid. In contrast, a similar analysis of urinary radioactivity after [2(-14)C]urate infusion revealed that more than 70% of the 14C was excreted as allantoin and not as uric acid.

Renal tubular permeability during increased intrarenal pressure.

Renal tubular permeability was studied by microinjection techniques during increased intrarenal pressure in anesthetized diuretic rats. Intrarenal pressure, as evidenced by intratubular pressure (ITP), was increased by elevation of ureteral pressure, partial renal venous constriction, or massive saline diuresis. Various combinations of radioactive inulin, creatinine, mannitol, sucrose, and iothalamate in isotonic saline were microinjected into superficial proximal and distal convolutions, and recovery of the isotopes was measured in the urine. Inulin was completely recovered in the urine from the injected kidney at both normal and elevated ITP. Creatinine, mannitol, sucrose, and iothalamate were also completely recovered at normal ITP, but recoveries were significantly lower, averaging 73, 85, 89, and 85%, respectively, after early proximal injection when proximal ITP was increased to 30+/-2 mm Hg by elevation of ureteral pressure. Since transit time is prolonged under these conditions, mannitol recovery was also studied during aortic constriction, which prolongs transit time but lowers ITP. Recovery was complete. A significant loss of mannitol was observed during massive saline diuresis, which shortens transit time but increases ITP. During renal venous constriction producing a proximal ITP of 30+/-2 mm Hg, mannitol recovery was significantly less than 100% even after microinjection into distal convolutions, but the loss was greater injection at more proximal puncture sites. Mannitol recovery was complete during elevation of ureteral pressure in the contralateral kidney. These studies demonstrate a change in the permeability characteristics of all major segments of the renal tubule during elevation of intrarenal pressure. This change is rapidly reversible and does not appear to be due to a humoral factor which gains access to the general circulation.

Urate-2-14C transport in the rat nephron.

Intrarenal transport of urate-2-(14)C was studied in anesthetized rats using the microinjection technic. During saline diuresis, small volumes of urate-2-(14)C (0.24-0.48 mM) and inulin-(3)H were injected into surface proximal and distal convoluted tubules, and ureteral urine was collected serially. Total (74-96%) and direct (57-84%) urate recovery increased significantly the more distal the puncture site. Delayed recovery (+/-20%) remained approximately the same regardless of localization of the microinjection. After proximal injections, total and direct recoveries of urate-2-(14)C were significantly higher in rats treated with probenecid, pyrazinoate, or PAH than during saline diuresis alone, while the excretion rates were comparable after distal injection. Delayed recovery was not altered by drug administration. The decreased proximal reabsorption of urate is presumably due to an effect of the drugs on the luminal membrane of the nephron. For perfusion at high urate concentrations, nonradioactive urate was added to the injectate (0.89-1.78 mM). Urate-2-(14)C recovery was almost complete and there was no delayed excretion, demonstrating saturation kinetics. These findings are compatible with a carrier-mediated mechanism for urate transport probably located at the luminal border of the proximal tubular epithelium. No definitive evidence for urate secretion was found in these studies.