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Reduced cortical renal GLUT1 expression induced by angiotensin-converting enzyme inhibition in diabetic spontaneously hypertensive rats

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Reduced cortical renal GLUT1 expression induced by angiotensin-converting enzyme inhibition in diabetic spontaneously hypertensive rats

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Título Reduced cortical renal GLUT1 expression induced by angiotensin-converting enzyme inhibition in diabetic spontaneously hypertensive rats
Autor Souza, M. S.
Machado, Ubiratan Fabres
Okamoto, Maristela Mitiko
Bertoluci, Marcello Casaccia
Ponpermeyer, C.
Leguisamo, Natalia Motta
Azambuja, Felipe
Irigoyen, Maria Claudia Costa
Schaan, Beatriz D'Agord
Abstract Diabetes in spontaneously hypertensive rats is associated with cortical renal GLUT1 and GLUT2 overexpression. Our objective was to evaluate the effect of the angiotensin-converting enzyme blockade on cortical renal GLUT1 and GLUT2 expression, urinary albumin and urinary TGF-β1. Streptozotocin, 50 mg/kg, or citrate buffer (N = 16) was administered as a single injection into the tail vein in adult spontaneously hypertensive rats (~260 g). Thirty days later, these diabetic spontaneously hypertensive rats received ramipril by gavage: 0.01 mg·kg-1·day-1 (D0.01, N = 14), 1 mg·kg-1·day-1 (D1, N = 9) or water (D, N = 11) for 15 days. Albumin and TGF-β1 (24-h urine), direct arterial pressure, renal tissue angiotensin-converting enzyme activity (fluorometric assay), and GLUT1 and GLUT2 protein levels (Western blot, renal cortex) were determined. Glycemia and glycosuria were higher (P < 0.05) in the diabetic rats compared with controls, but similar between the diabetic groups. Diabetes in spontaneously hypertensive rats lowered renal tissue angiotensin-converting enzyme activity (40%), which was reduced further when higher ramipril doses were used. Diabetes associated with hypertension raised GLUT1 by 28% (P < 0.0001) and GLUT2 by 76% (P = 0.01), and both doses of ramipril equally reduced cortical GLUT1 (D vs D1 and vs D0.01, P ≤ 0.001). GLUT2 levels were reduced in D0.01 (P < 0.05 vs D). Diabetes increased urinary albumin and TGF-β1 urinary excretion, but the 15-day ramipril treatment (with either dose) did not reduce them. In conclusion, ramipril is effective in lowering renal tissue angiotensin-converting enzyme activity, as well as blocking cortical GLUT1 overexpression, which may be beneficial in arresting the development of diabetic nephropathy.
Contido em Brazilian journal of medical and biological research = Revista brasileira de pesquisas médicas e biológicas. RiBeirão Preto, SP. Vol. 41, n. 11 (Nov. 2008), p. 960-968
Assunto Diabetes mellitus
Hipertensão
Inibidores da enzima conversora da angiotensina
[en] Angiotensin-converting enzyme inhibition
[en] Diabetic nephropathy
[en] Glucose transporter proteins
[en] Hypertension
[en] Streptozotocin
Origem Nacional
Tipo Artigo de periódico
URI http://hdl.handle.net/10183/21227
Arquivos Descrição Formato
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