ACE inhibition preserves heparan sulfate proteoglycans in the glomerular basement membrane of rats with established adriamycin nephropathy.
The gradual onset of the antiproteinuric effects of ACE inhibition suggests that structural effects on the glomerular basement membrane (GBM) may be involved in their renoprotective action. To test this hypothesis, we studied the effects of lisinopril (5 mg/kg/24 h) on proteinuria, focal glomerulosclerosis (FGS) and glomerular heparan sulfate (HS) proteoglycan (HSPG) GBM staining in rats with established Adriamycin nephrosis. Treatment was started 6 weeks after disease induction. As expected, lisinopril reduced blood pressure, proteinuria and the FGS score. In control rats, Adriamycin nephrosis was associated with significantly impaired GBM staining for both HSPG core protein (assessed from BL-31 staining) and HS staining (assessed from JM-403 staining) 12 weeks after disease induction. In rats treated with lisinopril (5 mg/kg/24 h) GBM staining was significantly better preserved for HS as well as for HSPG core protein. These data suggest that structural effects on the GBM, improving glomerular permselectivity, may be involved in the renoprotective effects of ACE inhibition in proteinuria-induced renal damage.
Wapstra
F H
FH
Division of Nephrology, Groningen University Institute for Drug Exploration, Nijmegen, The Netherlands.
Navis
G J
GJ
van Goor
H
H
van den Born
J
J
Berden
J H
JH
de Jong
P E
PE
de Zeeuw
D
D
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001485:Basement Membrane / Q000187:drug effects / Q000378:metabolism; D004317:Doxorubicin; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism*; D017706:Lisinopril / Q000494:pharmacology*; D008297:Male; D009401:Nephrosis / Q000378:metabolism* / Q000473:pathology / Q000652:urine; D011507:Proteinuria / Q000652:urine; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D019812:Heparan Sulfate Proteoglycans; D004317:Doxorubicin; D017706:Lisinopril