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

Journal Article · Sat Jun 01 04:00:00 EDT 1985 · Lab. Invest.; (United States)

OSTI ID:5244187

Keane, W F; Raij, L

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), Journal Name: Lab. Invest.; (United States) Vol. 6; ISSN LAINA
• Country of Publication: United States
• Language: English

Related Subjects

550901* -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANGIOTENSIN
ANIMALS
BETA DECAY RADIOISOTOPES
BIOLOGICAL LOCALIZATION
BIOLOGICAL MATERIALS
BIOLOGICAL MODELS
BLOOD
BODY
BODY FLUIDS
CARDIOVASCULAR AGENTS
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DISEASES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
GLANDS
GLOBULINS
GLOMERULI
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPES
KIDNEYS
LIVER
MAMMALS
MATERIALS
MOLECULES
NUCLEI
NUCLEOSIDES
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PERMEABILITY
PROTEINS
RADIOISOTOPES
RATS
RIBOSIDES
RODENTS
SPLEEN
UPTAKE
UROGENITAL SYSTEM DISEASES
VASOCONSTRICTORS
VERTEBRATES