Mesangial Function in Ureteral Obstruction in the Rat: <i>BLOCKADE OF THE EFFERENT LIMB</i>

Leopoldo Raij; William F. Keane; Hartmuth Osswald; Alfred Michael

doi:10.1172/JCI109574

Mesangial Function in Ureteral Obstruction in the Rat: BLOCKADE OF THE EFFERENT LIMB

Leopoldo Raij, William F. Keane, Hartmuth Osswald, and Alfred Michael

Published November 1, 1979 - More info

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Abstract

The kinetics for mesangial uptake and transport of radiolabeled aggregated human immunoglobulin (Ig)G (AHIgG¹²⁵I) deviated markedly from normal in male Sprague-Dawley rats with ureteral obstruction. Four experimental groups, each containing 25 rats, were used: (a) bilateral ureteral ligation (BUL) with release of one ureter 24 h later; (b) unilateral ureteral ligation with release 24 h later [UUL(R)]; (c) unilateral ureteral ligation without release (unreleased) [UUL(U)]; (d) uremia-control, which consisted of rats with ligated left ureter and a severed right ureter. A similar number of sham-operated rats served as control for each group. AHIgG¹²⁵I (45 mg/100 g body wt) was given intravenously 1 h after release of the ureteral obstruction (25 h after ureteral obstruction or sham surgery). Groups of five control and five experimental animals were sacrificed at 2, 4, 8, 16, and 24 h after injection.

At all time intervals, concentrations of AHIgG¹²⁵I in isolated glomeruli from control animals were similar to values obtained from nonobstructed kidneys of UUL(U) and UUL(R) rats: a linear decrease in concentration over a period of 24 h was observed when the logarithm of glomerular AHIgG¹²⁵I concentration was plotted against time. Aberrations in the kinetics were apparent in obstructed kidneys but not in liver, spleen, or blood concentrations of AHIgG¹²⁵I: (a) At 2 h in all obstructed kidneys, glomerular concentration of AHIgG¹²⁵I was markedly reduced. (b) In BUL (released or unreleased), glomerular concentrations of AHIgG¹²⁵I from 4 to 16 h were ≅ 10-fold those in UUL(U) or UUL(R) kidneys. (c) The significant decline in glomerular concentration between 4 and 16 h in control and nonobstructed kidneys was not observed in UUL(R), UUL(U), or BUL (released or unreleased) kidneys; in all obstructed kidneys, a plateau in glomerular concentrations of AHIgG¹²⁵I was observed between 4 and 16 h. (d) After 16 h at a time when the blood level of AHIgG¹²⁵I had decreased to 3% of initial values, there was progressive fall in glomerular AHIgG¹²⁵I. Similar results were obtained in the uremia-control group in rats, which indicated that uremia per se had no measurable effect on mesangial kinetics. These studies demonstrate that ureteral occlusion induces alterations in mesangial uptake (afferent limb) and egress (efferent limb) of macromolecules. Particularly evident is the “blockade” of the efferent limb which is demonstrable at high blood levels of AHIgG¹²⁵I. These alterations in the transit of macromolecules through the mesangium may be mediated in part by the hemodynamic changes that accompany ureteral obstruction.