title: Postnatal renal abnormalities in rats exposed to losartan during lactation.
abstract: OBJECTIVE
  Rats exposed to losartan during lactation exhibit progressive changes in renal function and structure. This study analyzed the early events in pups from dams that received losartan during lactation.
  
  
  METHODS
  Male Wistar rats from dams that received 2% sucrose (control, n = 25) or losartan (100 mg/kg/day) diluted in 2% sucrose (n = 33) during lactation were anesthetized 21 days after birth. Blood and urine samples were collected to assess renal function, and kidneys were removed for histological, immunohistochemical, Western blot, lipid peroxidation and glutathione analyses.
  
  
  RESULTS
  The group exposed to losartan exhibited increased albuminuria and fractional sodium and potassium excretion, decreased glomerular area and interstitial expansion. Immunohistochemical analyses demonstrated increased tubulointerstitial macrophage infiltration, apoptosis and increased vimentin and α-smooth-muscle-actin expression in animals exposed to losartan. In addition, the glomeruli of animals exposed to losartan exhibited increased peripheral desmin expression and reduced glomerular epithelial protein 1 and podocin expression compared to controls. Lastly, renal lipid peroxidation and glutathione levels were higher in the losartan-treated pups.
  
  
  CONCLUSIONS
  Pups exposed to losartan during lactation exhibited adverse changes in renal function and structure, and tubulointerstitial inflammation at 21 days of age that were associated with apoptosis and oxidative stress.
authors.affiliation: Department of Physiology, University of São Paulo, School of Medicine, Ribeirão Preto, Brazil.
authors.forename: Evelyn Cristina Santana
authors.initials: EC
authors.lastname: Marin
authors.forename: Heloísa Della Coletta
authors.initials: HD
authors.lastname: Francescato
authors.forename: Cleonice Giovanini Alves
authors.initials: CG
authors.lastname: da Silva
authors.forename: Roberto Silva
authors.initials: RS
authors.lastname: Costa
authors.forename: Terezila Machado
authors.initials: TM
authors.lastname: Coimbra
mesh_terms: D000199:Actins / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage* / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D003893:Desmin / Q000378:metabolism; D005260:Female; D007668:Kidney / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology; D007774:Lactation; D015227:Lipid Peroxidation / Q000187:drug effects; D019808:Losartan / Q000008:administration & dosage* / Q000633:toxicity*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: D000199:Actins; D047228:Angiotensin II Type 1 Receptor Blockers; D003404:Creatinine; D003893:Desmin; D019808:Losartan; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D014746:Vimentin; C498862:Acta2 protein, rat; C516891:Ptpro protein, rat