Renoprotective effects of valsartan and enalapril in STZ-induced diabetes in rats.
Effects of the angiotensin II type 1 (AT1) receptor antagonist valsartan and the angiotensin-converting enzyme (ACE) inhibitor enalapril were studied in streptozotocine (STZ)-induced diabetes in rats on the basis of microalbuminuria (Ma) and renal morphology. Five groups of Wistar rats were used, one group was the non-diabetic control, one group consisted of untreated STZ-diabetics and 3 groups of STZ-diabetics were treated with either enalapril and/or valsartan for 30 days. Blood glucose (BG) and Ma levels, body and kidney weight and glomerular size were measured. Immunohistochemical staining with an anti-transforming growth factor-beta1 (TGF-beta1) antibody was performed as well. In STZ-diabetics, BG and Ma levels were significantly increased when compared with the non-diabetic group. Although Ma levels in the valsartan-treated group was found to be higher than those in the non-diabetics group after 15 days of treatment, in all treated diabetic groups Ma levels were significantly decreased as compared with STZ-diabetics at the end of the experiment. Thickening of the glomerular and tubular basement membranes, increased mesangial matrix and glomerular size were found in the untreated diabetic group. All these changes were less in the treated groups. A significant increase in TGF-beta1 immunoreactivity was found in glomeruli of untreated STZ-diabetics as compared with non-diabetics. Again, TGF-beta1 expression was decreased in the treated groups as compared with untreated STZ-diabetics. We conclude that valsartan and enalapril have renoprotective effects in diabetic nephropathy. A combined therapy has an advantage because lower dosages of these drugs can be used. Their beneficial effects are related to a blockade of the renin-angiotensin system (RAS) and a decrease in TGF-beta1 expression in glomeruli.
Kalender
Betül
B
Department of Nephrology, Faculty of Medicine, University of Kocaeli, Turkey. bkalender@hotmail.com
Oztürk
Melek
M
Tunçdemir
Matem
M
Uysal
Omer
O
Dagistanli
Fatma Kaya
FK
Yegenaga
Itir
I
Erek
Ekrem
E
D000419:Albuminuria / Q000517:prevention & control; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000473:pathology* / Q000517:prevention & control*; D004656:Enalapril / Q000627:therapeutic use*; D005260:Female; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000068756:Valsartan
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001786:Blood Glucose; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D016212:Transforming Growth Factor beta; D004656:Enalapril; D000068756:Valsartan; D014633:Valine