Renal GLUT1 reduction depends on angiotensin-converting enzyme inhibition in diabetic hypertensive rats
| Autor: | Ubiratan Fabres Machado, Beatriz D'Agord Schaan, Maria C. Irigoyen, Ariel Silveira da Silva, Melissa Medeiros Markoski, Lucinara Dadda Dias, Julia Borges, Martina Schaan de Souza |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Ramipril medicine.medical_specialty Glucose transporter proteins Renal cortex Urinary system Down-Regulation Diabetic nephropathy Kidney General Biochemistry Genetics and Molecular Biology Diabetes Mellitus Experimental Pharmacology Toxicology and Pharmaceutics(all) Diabetes mellitus Rats Inbred SHR Internal medicine Angiotensin-converting enzyme inhibitors medicine Animals Amlodipine General Pharmacology Toxicology and Pharmaceutics Glucose Transporter Type 1 biology business.industry Streptozotocin Biochemistry Genetics and Molecular Biology(all) Angiotensin-converting enzyme General Medicine medicine.disease Rats FISIOLOGIA Blood pressure Endocrinology medicine.anatomical_structure Hypertension biology.protein business medicine.drug |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| Popis: | 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 (50 mg/kg). Thirty days later, animals received ramipril 15 μg/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-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). 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 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 GLUT1 content (C: 46.81 ± 4.54; A: 40.30 ± 5.39 and R: 26.89 ± 0.79 AU) decreased only in R ( p p p 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. |
| Databáze: | OpenAIRE |
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