Reduced cortical renal GLUT1 expression induced by angiotensin-converting enzyme inhibition in diabetic spontaneously hypertensive rats.
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.
Souza
M S
MS
Instituto de Cardiologia do Rio Grande do Sul, Fundação Universitária de Cardiologia, Porto Alegre, RS, Brasil.
Machado
U F
UF
Okamoto
M
M
Bertoluci
M C
MC
Ponpermeyer
C
C
Leguisamo
N
N
Azambuja
F
F
Irigoyen
M C
MC
Schaan
B D
BD
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
D000806:Angiotensin-Converting Enzyme Inhibitors; D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D053773:Transforming Growth Factor beta1; D005947:Glucose; D017257:Ramipril