Effect of parathyroid hormone on renal tubular permeability

The effect of parathyroid hormone (PTH) on renal tubular permeability has been studied utilizing micropuncture techniques in the rat kidney. After microinjection into superificial nephrons during control conditions, inulin (98.8 +/- 2.7%) and mannitol (97.2 +/- 2.4%) recovery from the experimental kidney was essentially complete. During intravenous infusion of PTH, inulin (99.3 +/- 2.9%) recovery was again complete. Mannitol recovery decreased signficantly after both early-proximal (84.7 +/- 5.8%, P less than 0.001) and late-proximal (89.7 +/- 2.8%, P less than 0.001) injections. There was no loss of either mannitol or inulin following distal tubular injection. Late-proximal TF/P inulin ratios during control conditions were 2.10 +/- 0.20 and decreased insignificantly to 1.99 +/- 0.21 during PTH infusion. Late-proximal TF/P mannitol rations were 2.09 +/- 0.21 during control periods and during PTH infusion decreased significantly to 1.78 +/- 0.19 (P less than 0.001). These results indicate that PTH induces a change in proximal tubular permeability to a usually impermeable nonelectrolyte, mannitol. The effects of PTH on proximal tubular transport could be partially explained by this alteration in permeability, which would increase passive backflux of actively transported species and decrease net transport while having no effect on active transport.

Abnormal tubular permeability in hypothermic perfused kidneys

Isolated canine kidneys perfused with cryoprecipitated plasma at 15 degrees C exhibit unexpectedly low inulin clearance (CIn) and creatinine clearance (CCr) rates. CIn and CCr, as well as p-aminohoppurate (PAH) clearance, varied linearly with urine flow rate, whether the variations in urine flow were spontaneous or induced, either by elevating perfusion pressure or by adding mannitol to the perfusate. Retrograde intraureteral injection (RII) of an isotonic fluid containing dextran, inulin, and PAH, followed by a period of ureteral occlusion and subsequent serial recollection of the injected fluid, revealed that inulin and PAH, relative to dextran, were lost from distal tubular fluid. Similar experiments in anesthetized dogs indicated no loss of inulin or PAH from tubules of in situ kidneys. Renal venous perfusate, collected from isolated kidneys during the low pressure phase of the RII, contained the following percentages of the quantities injected intraluminally: dextran, 9.22%; inulin, 11.0%; and PAH, 22.0%. These data indicate that a low measured glomerular filtration rate in hypothermic perfused kidneys is partly due to diffusion of inulin or creatinine out of the tubular lumen.

Distal permeability to urate and effects of benzofuran derivatives in the rat kidney

Effects of benziodarone and benzbromarone on renal tubular permeability to urate-14C were investigated in anesthetized rats by microinjection and clearance experiments. Urate-14C and inulin-3H were injected into proximal and distal convolutions and their recovery was measured in urine collected serially. In control rats, total and direct recoveries were significantly lower after early proximal (72 and 52%, respectively) than after late proximal injections (83 and 63%), whereas distal recoveries were higher (94 and 69%). Delayed excretion (ca. 25%) did not change with site of injection. Total distal recoveries were always less than 100% (P smaller than 0.001) but increased to 98% at high loads. After proximal injections in drug-pretreated rats, total and direct recoveries increased significantly (P smaller than 0.001). Recoveries after distal injections did not change in benzbromarone-treated rats, whereas direct and delayed excretion, respectively, increased (87%) and decreased (9%) significantly (P smaller than 0.001) following benziodarone infusion. These findings demonstrate inhibition of proximal urate reabsorption by benzofuran derivatives. The results also suggest distal reabsorption of urate, presumably along the collecting ducts.

On the interaction of calcium, sodium, and water transport in the diuresing kidney

Diuresis was induced in cats by infusion of 3% glucose in 10% ethanol. When urine flow had stabilized at high levels a solution of the Ca salt of ethylenediaminetetraacetate (Na2CaEDTA) was infused as a control for the effect of the EDTA molecule on renal function. The infusion was then changed over to the same molar rate of Na2EDTA, which resulted in a 30% decrease in serum Ca levels. Ca was then repleted rapidly as CaCl2 given intravenously, and the infusion was shifted back to Na2CaEDTA. The decrease in extracellular Ca concentration was associated with a significant antidiuresis. In further experiments on anesthetized dogs, osmotic diuresis was induced either by (a) infusion of hyperosmotic mannitol solutions, which were then shifted over to hypertonic NaCl, or (b) the same solutions in reverse order. Ca excretion correlated in linear fashion with Na excretion, but not with total solute excretion or with filtration rate. When Ca was added to the mannitol infusion, Na excretion increased in linear relation to Ca. It is suggested that Ca (a) decreases tubular permeability for water reabsorption and (b) decreases Na reabsorption, while Na (c) decreases Ca reabsorption. Mechanisms a and b would appear to involve membrane transport directly in the proximal tubule.

Tracer microinjection studies of renal tubular permeability

Renal tubular permeability was studied in rats with a tracer microinjection technique in which radioactive inulin and another isotope were simultaneously microinjected into proximal or distal convoluted tubules during osmotic diuresis and their excretion by that kidney measured. Noninulin radioactivity excreted with a time course similar to that of inulin is termed direct recovery and that excreted more slowly, delayed recovery. The absence of inulin excretion by the contralateral kidney demonstrated that there was no transtubular efflux of this substance under these conditions. Inulin transit time averaged 0.84 min and 0.33 min following proximal and distal microinjection, respectively. Excreted sodium 22 molecules apparently followed closely the path of inulin molecules, since they appeared in the urine simultaneously. There was no delayed recovery of sodium 22. There was considerable direct and delayed recovery of urea-C14, indicating its diffusion into the tubular epithelial cells and subsequent return to the lumen. There was very little delayed and almost no direct recovery of tritiated water under these conditions in which physiologically maximally effective amounts of ADH were probably present. The injected quantity of isotope minus its direct recovery is believed to approximate its total tubular efflux.