title: Renal GLUT1 reduction depends on angiotensin-converting enzyme inhibition in diabetic hypertensive rats.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Diabetes was induced in spontaneously-hypertensive rats (~210 g) by streptozotocin (50mg/kg). Thirty days later, animals received ramipril 15 μg/kg/day (R, n=10), or amlodipine 10mg/kg/day (A, n=8,) or water (C, n=10) by gavage. After 30-day treatment, body weight, glycaemia, urinary albumin and TGF-β1 (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).
  
  
  RESULTS
  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; 1867 ± 3.7 and 202.2 ± 4.3 mmHg; 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/24h), and renal cortex GLUT1 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Instituto de Cardiologia do Rio Grande do Sul/Fundação Universitária de Cardiologia (IC/FUC), Porto Alegre, RS, Brazil.
authors.forename: Ariel S
authors.initials: AS
authors.lastname: da Silva
authors.forename: Lucinara D
authors.initials: LD
authors.lastname: Dias
authors.forename: Júlia F
authors.initials: JF
authors.lastname: Borges
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Markoski
authors.forename: Martina S
authors.initials: MS
authors.lastname: de Souza
authors.forename: Maria C
authors.initials: MC
authors.lastname: Irigoyen
authors.forename: Ubiratan F
authors.initials: UF
authors.lastname: Machado
authors.forename: Beatriz D
authors.initials: BD
authors.lastname: Schaan
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D006973:Hypertension / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D051272:Glucose Transporter Type 1; C495679:Slc2a1 protein, rat