Souza M S, Machado U F, Okamoto M, Bertoluci M C, Ponpermeyer C, Leguisamo N, Azambuja F, Irigoyen M C, Schaan B D
Instituto de Cardiologia do Rio Grande do Sul, Fundação Universitária de Cardiologia, Porto Alegre, RS, Brasil.
Braz J Med Biol Res. 2008 Nov;41(11):960-8. doi: 10.1590/s0100-879x2008001100004.
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.
自发性高血压大鼠的糖尿病与肾皮质葡萄糖转运蛋白1（GLUT1）和葡萄糖转运蛋白2（GLUT2）的过表达有关。我们的目的是评估血管紧张素转换酶抑制剂对肾皮质GLUT1和GLUT2表达、尿白蛋白和尿转化生长因子β1（TGF-β1）的影响。将50mg/kg链脲佐菌素或柠檬酸盐缓冲液（N = 16）单次尾静脉注射给成年自发性高血压大鼠（约260g）。30天后，这些糖尿病自发性高血压大鼠经口灌胃给予雷米普利：0.01mg·kg⁻¹·d⁻¹（D0.01，N = 14）、1mg·kg⁻¹·d⁻¹（D1，N = 9）或水（D，N = 11），持续15天。测定白蛋白和TGF-β1（24小时尿）、直接动脉压、肾组织血管紧张素转换酶活性（荧光测定法）以及GLUT1和GLUT2蛋白水平（蛋白质印迹法，肾皮质）。糖尿病大鼠的血糖和糖尿水平高于对照组（P < 0.05），但糖尿病组之间相似。自发性高血压大鼠的糖尿病降低了肾组织血管紧张素转换酶活性（40%），当使用更高剂量的雷米普利时，该活性进一步降低。高血压合并糖尿病使GLUT1升高28%（P < 0.0001），GLUT2升高76%（P = 0.01），两种剂量的雷米普利均能同等程度降低肾皮质GLUT1（D组与D1组及D0.01组相比，P ≤ 0.001）。D0.01组的GLUT2水平降低（与D组相比，P < 0.05）。糖尿病增加了尿白蛋白和TGF-β1的尿排泄，但15天的雷米普利治疗（任一剂量）均未使其降低。总之，雷米普利可有效降低肾组织血管紧张素转换酶活性，并阻断肾皮质GLUT1的过表达，这可能有助于阻止糖尿病肾病的发展。
