Relationship among altered glomerular barrier permselectivity, angiotensin II, and mesangial uptake of macromolecules

W. F. Keane, L. Raij

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

Clinical and experimental studies suggest that accumulation of phlogogenic macromolecules in the glomerular mesangium may lead to mesasngial expansion and eventual glomerulosclerosis. In focal glomerulosclerosis and nephrotic syndrome entrapment of macromolecules is observed in areas of glomerulosclerosis. To determine whether mesangial uptake of radiolabeled, heat-aggregated IgG (AG125I), a biologically active macromolecular protein, is influenced by increased glomerular filtration barrier permeability, we evaluated the glomerular uptake of AG125I in three models of proteinuria: (a) aminonucleoside of puromycin nephropathy (PAN), (b) adriamycin nephropathy, and (c) Heyman's nephropathy. Rats were studied approximately 1 week after onset of proteinuria. AG125I was measured in preparations of isolated glomeruli and compared to simultaneous blood, liver, and spleen levels. Only rats with PAN had a marked increase in glomerular AG125I compared to control rats, 7.8 versus 2.6 μg/mg of glomeruli, respectively. We then evaluated whether a continuous infusion of a competitive inhibitor of angiotensin II, saralasin (300 μg/kg of body weight/minute), influenced mesangial uptake of AG125I in PAN rats. Strikingly, glomerular AG125I in rats with PAN was reduced to levels comparable to that observed in control rats infused with only saralasin, 2.8 versus 3.0 μg/mg of glomeruli, respectively. This effect on glomerular AG125I content was independent of any significant effect of saralasin on blood, hepatic, or splenic levels of AG125I. Moreover, these changes in glomerular AG125I in saralasin-infused rats with PAN did not appear to directly correlate with changes in whole kidney function. These studies also demonstrated that proteinuria per se did not influence mesangial uptake of macromolecules. Thus, these data indicated that angiotensin II had an important effect on intraglomerular factors that modulate mesangial localization of phlogogenic macromolecules.

Original languageEnglish (US)
Pages (from-to)599-604
Number of pages6
JournalLaboratory Investigation
Volume52
Issue number6
StatePublished - 1985

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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