Effect of angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade on streptozotocin-induced diabetic nephropathy.
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 T(1) (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 Q&Irb), 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 Q&Irb-treated groups were given Q (in a dose of 3 mg/kg body weight), Irb (5 mg/kg body weight), and Q&Irb (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).
Sen
Saniye
S
Department of Nephrology, Faculty of Medicine, Trakya University, Edirne, Turkey.
Saniye
Sen
S
Kanter
Mehmet
M
Mehmet
Kanter
K
Ustundag
Sedat
S
Sedat
Ustundag
U
Aktas
Cevat
C
Cevat
Aktas
A
Dogutan
Haluk
H
Yalcin
Omer
O
Omer
Yalcin
Y
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000473:pathology; D004359:Drug Therapy, Combination; D005260:Female; D007150:Immunohistochemistry; D000077405:Irbesartan; D007668:Kidney / Q000378:metabolism / Q000648:ultrastructure; D007677:Kidney Function Tests; D000077583:Quinapril; D051381:Rats; D017207:Rats, Sprague-Dawley; D044005:Tetrahydroisoquinolines / Q000627:therapeutic use*; D013777:Tetrazoles / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D044005:Tetrahydroisoquinolines; D013777:Tetrazoles; D053773:Transforming Growth Factor beta1; D000077405:Irbesartan; D000077583:Quinapril