This study was undertaken to determine the role of
angiotensin II (AII) in the development of glomerulosclerosis, using an AII receptor antagonist in an animal model of
hyperlipidemia. Hyperlipidemic Imai rats were employed because they spontaneously develop glomerulosclerosis; this is especially true in males. Group 1 (n = 5) received no specific
therapy. Group 2 (n = 5) was treated with
enalapril at a dosage of 50 mg/l in
drinking water starting at 6 weeks of age. Group 3 (n = 5) and group 4 (n = 6) were treated with the AII receptor antagonist
DuP 753 at a respective dosage of 15 mg/l (low-dose DuP) and 150 mg/l (high-dose DuP) in
drinking water.
Body weight, blood pressure, urinary
protein, serum albumin,
cholesterol, BUN and serum
creatinine were measured and compared among the groups from 12 to 24 weeks of age.
Enalapril and high-dose DuP were almost equally effective in controlling systemic
hypertension. Each treatment significantly reduced
proteinuria (172 +/- 112 and 152 +/- 72 mg/kg/day at 24 weeks) as compared with that in the controls (421 +/- 147 mg/kg/day; p < 0.05 and p < 0.01, respectively).
Hypercholesterolemia also decreased (82 +/- 4 and 89 +/- 6 mg/dl) as compared with that of the controls (141 +/- 48 mg/dl; both p < 0.05). Glomerulosclerosis index (SI) was significantly higher in the untreated control rats (55 +/- 26) than in the
enalapril-treated rats (2 +/- 3; p < 0.005) and the high-dose-DuP-treated rats (6 +/- 6, p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)