title: Histopathological and ultrastructural effects of Losartan on embryonic rat kidney.
abstract: The aim of our study was to investigate the histopathological, immunohistochemical and ultrastructural effects of Losartan (a selective angiotensin II type-1 receptor blocker) on renal development in rats. Twelve pregnant rats were divided into control and experimental groups. In the experimental group, Losartan (10 mg/kg/day) was given via nasogastric tube, between the sixth day of implantation and time of sacrifice on embryonic days 18 and 20. All formalin-fixed, paraffin wax-embedded renal tissue sections were stained with hematoxylin and eosin or labelled for binding of primary antibodies against transforming growth factor-beta (TGF-beta 1,-2,-3) using an avidin-biotin-peroxidase method. For electron microscopic examination, samples were fixed with glutaraldehyde and osmium tetroxide and embedded in araldite. Glomerular basement membrane (GBM) thickness was measured and compared using an unpaired t-test. Angiotensin II type-1 receptor antagonism by Losartan inhibited renal growth and delayed nephron maturation. Increased immunoreactivity of TGF-beta's was observed in developing nephron precursors and interstitial cells in the experimental group. Electron microscopical examination showed that thickening of the GBM was normal in the control group but an irregular thickening was seen in the experimental group (p < 0.001). It was also seen that epithelial cells of developing tubules underwent apoptosis in the experimental group. Thus, renal development in rats seems to depend on an intact renin-angiotensin system.
authors.affiliation: Department of Pediatric Nephrology, Faculty of Medicine, Celal Bayar University, Manisa, Turkey. ipek.akil@bayer.edu.tr
authors.forename: Ipek
authors.initials: I
authors.lastname: Akil
authors.forename: Sevinc
authors.initials: S
authors.lastname: Inan
authors.forename: Beyhan
authors.initials: B
authors.lastname: Gurcu
authors.forename: Aysegul
authors.initials: A
authors.lastname: Nazikoglu
authors.forename: Kemal
authors.initials: K
authors.lastname: Ozbilgin
authors.forename: Sevda
authors.initials: S
authors.lastname: Muftuoglu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D050533:Glomerular Basement Membrane / Q000187:drug effects / Q000648:ultrastructure; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects* / Q000196:embryology / Q000648:ultrastructure*; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods; D008854:Microscopy, Electron / Q000379:methods; D009399:Nephrons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000276:immunology
chemical_list: D044140:Receptor, Angiotensin, Type 1; D016212:Transforming Growth Factor beta; D019808:Losartan