Losartan preserves glomerular basement membrane anionic charge sites in a rat model of nephropathy.
BACKGROUND
Disruption of the size and charge selectivity of the glomerular basement membrane (GBM) leads to proteinuria. Blood pressure medications suppress proteinuria by preserving GBM function. We investigated the mechanism of losartan, an angiotensin II receptor blocker (ARB), in a rat model of nephropathy.


METHODS
Male Wistar rats were given 25 mg/kg per day of losartan or the same volume of saline (control) from 5 days before, to 14 days after, induction of nephropathy by injection of puromycin aminonucleoside (PAN). Serum blood urea nitrogen (BUN) and creatinine, blood pressure, urinary protein, glomerular morphology and the number of GBM anionic sites were measured in the 2 groups on days 0, 7 and 14.


RESULTS
The losartan group had significantly lower urinary protein on days 7 and 14, and higher BUN on day 14, but there were no significant differences between the losartan and control groups in serum creatinine or blood pressure. Light microscopy indicated reduced mesangial cell proliferation and expansion of the mesangial area in the losartan group relative to controls. There were more GBM anionic sites in the losartan group on days 7 and 14. In addition, all anionic sites on the surface of foot processes of epithelial cells disappeared in the control group but remained in the losartan group.


CONCLUSIONS
A rat model of nephropathy indicates that losartan reduces urinary protein and preserves the number of anionic sites on the GBM, but has no apparent effect on hemodynamics.
Department of Nephrology, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou, PR China. rabbityan127@yahoo.com.cn
Yan
Y
Liu
Daoyuan
D
Zhou
Xiao
X
Xiao
Danping
D
Qin
Xiaoshi
X
Zhong
Xuan
X
Xiong
Kiyoko
K
Inui
Ashio
A
Yoshimura
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000838:Anions / Q000378:metabolism*; D004195:Disease Models, Animal; D050533:Glomerular Basement Membrane / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D008854:Microscopy, Electron; D009404:Nephrotic Syndrome / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D047228:Angiotensin II Type 1 Receptor Blockers; D000838:Anions; D019808:Losartan