The effect of losartan and captopril on glomerular basement membrane anionic charge in a diabetic rat model

Objective Although angiotensin-converting enzyme inhibitors are known to re duce 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 wer e 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 con trol 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, seru m sialic acid, urinary glycosaminoglycan and albumin were measured and kidn ey 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 cell s) 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 sial ic acid levels (mg/dl) were 90.6 +/- 14.1 for group A, 45.6 +/- 6.8 for gro up B, 89.1 +/- 8.5 for group C, 50.8 +/- 6.4 for group D (A, C > D, P < 0.0 1; A > B P < 0.01). Albuminuria (mu g/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 album inuria in a diabetic rat model. While captopril preserves basement membrane anionic charges, losartan has no effect. The anti-proteinuric effects of t hese drugs seem to have different mechanisms. I Hypertens 1999, 17:1217-122 3 (C) Lippincott Williams & Wilkins.