Renal GLUT1 reduction depends on angiotensin-converting enzyme inhibition in diabetic hypertensive rats

Abstract

Aims: Angiotensin-converting enzyme (ACE) inhibitors are used in diabetic kidney disease to reduce systemic/intra-glomerular pressure. The objective of this study was to investigate whether reducing blood pressure (BP) could modulate renal glucose transporter expression, and urinary markers of diabetic nephropathy in diabetic hypertensive rats treated with ramipril or amlodipine. Main methods: Diabetes was induced in spontaneously-hypertensive rats (similar to 210 g) by streptozotocin (50 mg/kg). Thirty days later, animals received ramipril 15 mu g/kg/day (R, n = 10), or amlodipine 10 mg/kg/day (A, n = 8,) or water (C, n = 10) by gavage. After 30-day treatment, body weight, glycaemia, urinary albumin and TGF-beta 1 (enzyme-linked immunosorbent assay) and BP (tail-cuff pressure method) were evaluated. Kidneys were removed for evaluation of renal cortex glucose transporters (Western blotting) and renal tissue ACE activity (fluorometric assay). Key findings: After treatments, body weight (p = 0.77) and glycaemia (p = 0.22) were similar among the groups. Systolic BP was similarly reduced (p < 0.001) in A and R vs. C (172.4 +/- 3.2; 186.7 +/- 3.7 and 202.2 +/- 4.3 mm Hg; respectively). ACE activity (C: 0.903 +/- 0.086; A: 0.654 +/- 0.025, and R: 0.389 +/- 0.057 mU/mg), albuminuria (C: 264.8 +/- 15.4; A: 140.8 +/- 13.5 and R: 102.8 +/- 6.7 mg/24 h), and renal cortex GLUM content (C: 46.81 +/- 4.54; A: 40.30 +/- 5.39 and R: 26.89 +/- 0.79 AU) decreased only in R (p < 0.001, p < 0.05 and p < 0.001; respectively). Significance: We concluded that the blockade of the renin-angiotensin system with ramipril reduced early markers of diabetic nephropathy, a phenomenon that cannot be specifically related to decreased BP levels.