title: Reduced cortical renal GLUT1 expression induced by angiotensin-converting enzyme inhibition in diabetic spontaneously hypertensive rats.
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-beta1. Streptozotocin, 50 mg/kg, or citrate buffer (N = 16) was administered as a single injection into the tail vein in adult spontaneously hypertensive rats (approximately 260 g). Thirty days later, these diabetic spontaneously hypertensive rats received ramipril by gavage: 0.01 mg x kg(-1) x day(-1) (D0.01, N = 14), 1 mg x kg(-1) x day(-1) (D1, N = 9) or water (D, N = 11) for 15 days. Albumin and TGF-beta1 (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 < or = 0.001). GLUT2 levels were reduced in D0.01 (P < 0.05 vs D). Diabetes increased urinary albumin and TGF-beta1 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.
authors.affiliation: Instituto de Cardiologia do Rio Grande do Sul, Fundação Universitária de Cardiologia, Porto Alegre, RS, Brasil.
authors.forename: M S
authors.initials: MS
authors.lastname: Souza
authors.forename: U F
authors.initials: UF
authors.lastname: Machado
authors.forename: M
authors.initials: M
authors.lastname: Okamoto
authors.forename: M C
authors.initials: MC
authors.lastname: Bertoluci
authors.forename: C
authors.initials: C
authors.lastname: Ponpermeyer
authors.forename: N
authors.initials: N
authors.lastname: Leguisamo
authors.forename: F
authors.initials: F
authors.lastname: Azambuja
authors.forename: M C
authors.initials: MC
authors.lastname: Irigoyen
authors.forename: B D
authors.initials: BD
authors.lastname: Schaan
mesh_terms: D000419:Albuminuria; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental; D005947:Glucose / Q000032:analysis; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D051273:Glucose Transporter Type 2 / Q000378:metabolism*; D007672:Kidney Cortex / Q000737:chemistry* / Q000187:drug effects; D008297:Male; D017257:Ramipril / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D053773:Transforming Growth Factor beta1 / Q000652:urine
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D053773:Transforming Growth Factor beta1; D005947:Glucose; D017257:Ramipril