Relationship among altered glomerular barrier permselectivity, angiotensin II, and mesangial uptake of macromolecules
Clinical and experimental studies suggest that accumulation of phlogogenic macromolecules in the glomerular mesangium may lead to mesangial 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 (AG/sup 125/I), a biologically active macromolecular protein, is influenced by increased glomerular filtration barrier permeability, the authors evaluated the glomerular uptake of AG/sup 125/I in three models of proteinuria: aminonucleoside of puromycin nephropathy (PAN), adriamycin nephropathy, and Heyman's nephropathy. Rats were studied approximately 1 week after onset of proteinuria. AG/sup 125/I 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 AG/sup 125/I compared to control rats, 7.8 versus 2.6 micrograms/mg of glomeruli, respectively. The authors then evaluated whether a continuous infusion of a competitive inhibitor of angiotensin II, saralasin (300 micrograms/kg of body weight/minute), influenced mesangial uptake of AG/sup 125/I in PAN rats. Strikingly, glomerular AG/sup 125/I in rats with PAN was reduced to levels comparable to that observed in control rats infused with only saralasin, 2.8 versus 3.0 micrograms/mg of glomeruli, respectively. This effect on glomerular AG/sup 125/I content was independent of any significant effect of saralasin on blood, hepatic, or splenic levels of AG/sup 125/I. Moreover, these changes in glomerular AG/sup 125/I in saralasin-infused rats with PAN did not appear to directly correlate with changes in whole kidney function.
- Research Organization:
- Hennepin County Medical Center, Minneapolis, MN
- OSTI ID:
- 5244187
- Journal Information:
- Lab. Invest.; (United States), Vol. 6
- Country of Publication:
- United States
- Language:
- English
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