Objective: Although angiotensin-converting enzyme inhibitors are known to reduce albuminuria by preserving glomerular basement membrane anionic content, the effects of angiotensin II receptor blockage are currently not known. The aim of this study was to evaluate the effects of captopril and losartan on glomerular basement membrane anionic charges in a diabetic rat model.
Design: After diabetes induction with streptozotocin, female Wistar rats were divided into three groups: group A, losartan 10 mg/kg by gavage (n = 8); group B, captopril 50 mg/l in drinking water (n = 6); group C, diabetic control rats (n = 8) given only tap water. Group D (eight rats) served as non-diabetic controls. At the end of 8 weeks, erythrocyte membrane charge, serum sialic acid, urinary glycosaminoglycan and albumin were measured and kidney specimens stained with Alcian blue in order to assess basement membrane glycosaminoglycans.
Results: Red blood cell anionic charges (ng Alcian blue/ 10(6) red blood cells) were 371.5+/-9.9 for group A, 443.5+/-7.1 for group B, 400.1+/-14.7 for group C, 468.7+/-4 for group D (A<D, C<D, P<0.01). Serum sialic acid levels (mg/dl) were 90.6+/-14.1 for group A, 45.6+/-6.8 for group B, 89.1+/-8.5 for group C, 50.8+/-6.4 for group D (A, C>D, P<0.01; A>B P<0.01). Albuminuria (microg/day) was 778+/-221 for group A, 719+/-314 for group B, 1724+/-945 for group C, 393+/-263 for group D (A, B<C, P<0.05). Urinary glycosaminoglycan/creatinine ratio was 14.2+/-1.1 for group A, 9.9+/-1 for group B; 28.3+/-8 for group C, 5.5+/-1.7 for group D (B<C, P<0.001; B<A, P<0.003). Alcian blue staining was 1.8+/-0.2, 2.2+/-0.4, 1.5+/-0.16, 2.8+/-0.2 for groups A, B, C and D respectively (C, A<D P<0.05).
Conclusion: Losartan and captopril have comparable effects on reducing albuminuria in a diabetic rat model. While captopril preserves basement membrane anionic charges, losartan has no effect. The anti-proteinuric effects of these drugs seem to have different mechanisms.