Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1979 Nov;64(5):1204–1212. doi: 10.1172/JCI109574

Mesangial Function in Ureteral Obstruction in the Rat

BLOCKADE OF THE EFFERENT LIMB

Leopoldo Raij 1,2, William F Keane 1,2, Hartmuth Osswald 1,2, Alfred Michael 1,2
PMCID: PMC371265  PMID: 500807

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.

Full text

PDF
1204

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allison M. E., Lipham E. M., Gottschalk C. W. Hydrostatic pressure in the rat kidney. Am J Physiol. 1972 Oct;223(4):975–983. doi: 10.1152/ajplegacy.1972.223.4.975. [DOI] [PubMed] [Google Scholar]
  2. Azar S., Johnson M. A., Hertel B., Tobian L. Single-nephron pressures, flows, and resistances in hypertensive kidneys with nephrosclerosis. Kidney Int. 1977 Jul;12(1):28–40. doi: 10.1038/ki.1977.76. [DOI] [PubMed] [Google Scholar]
  3. Barajas L. The ultrastructure of the juxtaglomerular apparatus as disclosed by three-dimensional reconstructions from serial sections. The anatomical relationship between the tubular and vascular components. J Ultrastruct Res. 1970 Oct;33(1):116–147. doi: 10.1016/s0022-5320(70)90121-8. [DOI] [PubMed] [Google Scholar]
  4. Becker C. G. Demonstration of actomyosin in mesangial cells of the renal glomerulus. Am J Pathol. 1972 Jan;66(1):97–110. [PMC free article] [PubMed] [Google Scholar]
  5. Buerkert J., Alexander E., Purkerson M. L., Klahr S. On the site of decreased fluid reabsorption after release of ureteral obstruction in the rat. J Lab Clin Med. 1976 Mar;87(3):397–410. [PubMed] [Google Scholar]
  6. CHRISTIAN C. L. Studies of aggregated gamma-globulin. I. Sedimentation, electrophoretic and anticomplementary properties. J Immunol. 1960 Jan;84:112–116. [PubMed] [Google Scholar]
  7. Elema J. D., Hoyer J. R., Vernier R. L. The glomerular mesangium: uptake and transport of intravenously injected colloidal carbon in rats. Kidney Int. 1976 May;9(5):395–406. doi: 10.1038/ki.1976.49. [DOI] [PubMed] [Google Scholar]
  8. Gerber J. G., Data J. L., Nies A. S. Enhanced renal prostaglandin production in the dog. The effect of sodium arachidonate in nonfiltering kidney. Circ Res. 1978 Jan;42(1):43–45. doi: 10.1161/01.res.42.1.43. [DOI] [PubMed] [Google Scholar]
  9. Haakenstad A. O., Mannik M. Saturation of the reticuloendothelial system with soluble immune complexes. J Immunol. 1974 May;112(5):1939–1948. [PubMed] [Google Scholar]
  10. Haakenstad A. O., Mannik M. The disappearance kinetics of soluble immune complexes prepared with reduced and alkylated antibodies and with intact antibodies in mice. Lab Invest. 1976 Sep;35(3):283–292. [PubMed] [Google Scholar]
  11. Harris R. H., Yarger W. E. Renal function after release of unilateral ureteral obstruction in rats. Am J Physiol. 1974 Oct;227(4):806–815. doi: 10.1152/ajplegacy.1974.227.4.806. [DOI] [PubMed] [Google Scholar]
  12. Harris R. H., Yarger W. E. The pathogenesis of post-obstructive diuresis. The role of circulating natriuretic and diuretic factors, including urea. J Clin Invest. 1975 Oct;56(4):880–887. doi: 10.1172/JCI108167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. ISHIZAKA K., ISHIZAKA T. Biologic activity of aggregated gamma-globulin. II. A study of various methods for aggregation and species differences. J Immunol. 1960 Aug;85:163–171. [PubMed] [Google Scholar]
  14. Jaenike J. R. The renal functional defect of postobstructive nephyropathy. The effects of bilateral ureteral obstruction in the rat. J Clin Invest. 1972 Dec;51(12):2999–3006. doi: 10.1172/JCI107127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Källskog O., Lindbom L. O., Ulfendahl H. R., Wolgast M. Kinetics of the glomerular ultrafiltration in the rat kidney. An experimental study. Acta Physiol Scand. 1975 Nov;95(3):293–300. doi: 10.1111/j.1748-1716.1975.tb10053.x. [DOI] [PubMed] [Google Scholar]
  16. Leiper J. M., Thomson D., MacDonald M. K. Uptake and transport of Imposil by the glomerular mesangium in the mouse. Lab Invest. 1977 Nov;37(5):526–533. [PubMed] [Google Scholar]
  17. Mathew T. H., Kincaid-Smith P., Vikraman P. Risks of vesicoureteric reflux in the transplanted kidney. N Engl J Med. 1977 Aug 25;297(8):414–418. doi: 10.1056/NEJM197708252970803. [DOI] [PubMed] [Google Scholar]
  18. Mauer S. M., Fish A. J., Blau E. B., Michael A. F. The glomerular mesangium. I. Kinetic studies of macromolecular uptake in normal and nephrotic rats. J Clin Invest. 1972 May;51(5):1092–1101. doi: 10.1172/JCI106901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mauer S. M., Fish A. J., Day N. K., Michael A. F. The glomerular mesangium. II. Studies of macromolecular uptake in nephrotoxic nephritis in rats. J Clin Invest. 1974 Feb;53(2):431–439. doi: 10.1172/JCI107577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. McConahey P. J., Dixon F. J. A method of trace iodination of proteins for immunologic studies. Int Arch Allergy Appl Immunol. 1966;29(2):185–189. doi: 10.1159/000229699. [DOI] [PubMed] [Google Scholar]
  21. McDougal W. S., Wright F. S. Defect in proximal and distal sodium transport in post-obstructive diuresis. Kidney Int. 1972 Dec;2(6):304–317. doi: 10.1038/ki.1972.114. [DOI] [PubMed] [Google Scholar]
  22. Michael A. F., Fish A. J., Good R. A. Glomerular localization and transport of aggregated proteins in mice. Lab Invest. 1967 Jul;17(1):14–29. [PubMed] [Google Scholar]
  23. Morrison A. R., Nishikawa K., Needleman P. Thromboxane A2 biosynthesis in the ureter obstructed isolated perfused kidney of the rabbit. J Pharmacol Exp Ther. 1978 Apr;205(1):1–8. [PubMed] [Google Scholar]
  24. Nishikawa K., Morrison A., Needleman P. Exaggerated prostaglandin biosynthesis and its influence on renal resistance in the isolated hydronephrotic rabbit kidney. J Clin Invest. 1977 Jun;59(6):1143–1150. doi: 10.1172/JCI108738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Raij L., Keane W. F., Michael A. F. Unilateral Shwartzman reaction: cortical necrosis in one kidney following in vivo perfusion with endotoxin. Kidney Int. 1977 Aug;12(2):91–95. doi: 10.1038/ki.1977.85. [DOI] [PubMed] [Google Scholar]
  26. Scheinman J. I., Fish A. J., Michael A. F. The immunohistopathology of glomerular antigens. The glomerular basement membrane, collagen, and actomyosin antigens in normal and diseased kidneys. J Clin Invest. 1974 Nov;54(5):1144–1154. doi: 10.1172/JCI107858. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Schnermann J., Osswald H., Hermle M. Inhibitory effect of methylxanthines on feedback control of glomerular filtration rate in the rat kidney. Pflugers Arch. 1977 May 6;369(1):39–48. doi: 10.1007/BF00580808. [DOI] [PubMed] [Google Scholar]
  28. Striker G. E., Mannik M., Tung M. Y. Role of marrow-derived monocytes and mesangial cells in removal of immune complexes from renal glomeruli. J Exp Med. 1979 Jan 1;149(1):127–136. doi: 10.1084/jem.149.1.127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wilson D. R. Renal function during and following obstruction. Annu Rev Med. 1977;28:329–339. doi: 10.1146/annurev.me.28.020177.001553. [DOI] [PubMed] [Google Scholar]
  30. Yarger W. E., Aynedjian H. S., Bank N. A micropuncture study of postobstructive diuresis in the rat. J Clin Invest. 1972 Mar;51(3):625–637. doi: 10.1172/JCI106852. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES