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Renal GLUT1 reduction depends on angiotensin-converting enzyme inhibition in diabetic hypertensive rats.
da Silva, Ariel S; Dias, Lucinara D; Borges, Júlia F; Markoski, Melissa M; de Souza, Martina S; Irigoyen, Maria C; Machado, Ubiratan F; Schaan, Beatriz D.
Afiliação
  • da Silva AS; Instituto de Cardiologia do Rio Grande do Sul/Fundação Universitária de Cardiologia (IC/FUC), Porto Alegre, RS, Brazil.
Life Sci ; 92(24-26): 1174-9, 2013 Jul 10.
Article em En | MEDLINE | ID: mdl-23680377
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 (~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-ß1 (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; 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). 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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Inibidores da Enzima Conversora de Angiotensina / Diabetes Mellitus Experimental / Transportador de Glucose Tipo 1 / Hipertensão Limite: Animals Idioma: En Revista: Life Sci Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Inibidores da Enzima Conversora de Angiotensina / Diabetes Mellitus Experimental / Transportador de Glucose Tipo 1 / Hipertensão Limite: Animals Idioma: En Revista: Life Sci Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda