Effect of Angiotensin-Converting Enzyme Inhibition and Angiotensin II Type 1 Receptor Blockade on Streptozotocin-Induced Diabetic Nephropathy


Şen S., KANTER M., Üstündağ S., Aktaş C., Doğutan H., Yalçın Ö.

RENAL FAILURE, cilt.30, ss.1023-1033, 2008 (SCI İndekslerine Giren Dergi)

  • Cilt numarası: 30 Konu: 10
  • Basım Tarihi: 2008
  • Doi Numarası: 10.1080/08860220802495248
  • Dergi Adı: RENAL FAILURE
  • Sayfa Sayısı: ss.1023-1033

Özet

The aim of this study was designed to investigate the possible beneficial effects of the angiotensin-converting enzyme (ACE) inhibitor, Quinapril (Q) and, the angiotensin (ang) II T1 (AT1) receptor blocker, irbesartan (Irb), in streptozotocin (STZ)-induced diabetes in rats. The rats were randomly allotted into one of five experimental groups: A (control), B (diabetic untreated), C (diabetic treated with Q), D (diabetic treated with Irb), and E (diabetic treated with QIrb), each group containing 10 animals. Groups B-E received STZ. Diabetes was induced in four groups by a single intraperitoneal (i.p) injection of STZ (50 mg/kg, freshly dissolved in 5 mmol/L citrate buffer, pH 4.5). Two days after STZ treatment, development of diabetes in four experimental groups was confirmed by measuring blood glucose levels in a tail vein blood samples. Rats with blood glucose levels of 250 mg/dL or higher were considered to be diabetic. The rats in Q-, Irb-, and QIrb-treated groups were given Q (in a dose of 3 mg/kg body weight), Irb (5 mg/kg body weight), and QIrb (in a dose of 1.5 mg/kg + 2.5 mg/kg body weight) once a day orally by using intra-gastric intubation for 12 weeks starting two days after STZ injection. Treatment of Q and especially Irb reduced the glomerular size and thickening of capsular, glomerular, and tubular basement membranes; and increased amounts of mesangial matrix and tubular dilatation and renal function as compared with diabetics untreated. Notably, the better effects were obtained when Q and Irb given together. We conclude that Q, Irb, and especially Q+Irb therapy causes renal morphologic and functional improvement after STZ-induced diabetes in rats. We believe that further preclinical research into the utility of Q and Irb treatment, alone or its combination, may indicate its usefulness as a potential treatment in diabetic nephropathy (DNp).