title: Tenofovir during pregnancy in rats: a novel pathway for programmed hypertension in the offspring.
abstract: OBJECTIVE
  To evaluate the occurrence of systemic and renal abnormalities in the offspring of Wistar rats exposed to tenofovir disoproxil fumarate (DF) during pregnancy.
  
  
  METHODS
  Female Wistar rats received a standard diet, with or without addition of tenofovir DF (100 mg/kg diet), 1 week before mating and during pregnancy. Offspring from the tenofovir DF group were placed with an untreated foster mother during breastfeeding and compared with offspring from rats maintained on a standard diet during mating and pregnancy (control). Control and tenofovir DF were followed up at 3 and 6 months of age. Monthly body weight and systolic blood pressure (SBP), glomerular counts, renal function, biochemical parameters, angiotensin II, renal renin angiotensin aldosterone system (RAAS) and renal sodium transporters were analysed.
  
  
  RESULTS
  Tenofovir DF offspring showed lower birth weight compared with the control group. After the third month, growth among the tenofovir DF group experienced a rapid catch-up. SBP increased progressively after the second month of age in the tenofovir DF group. Nephron number did not differ between the groups; however, the tenofovir DF group showed glomerular structural changes. Plasma aldosterone was higher in the tenofovir DF group, associated with a significant increase in renal expression of RAAS. The tenofovir DF rats showed up-regulation of renal sodium transporters and consequently lower urinary sodium excretion.
  
  
  CONCLUSIONS
  This is the first demonstration using an experimental model that maternal exposure to tenofovir DF during gestation results in overactivation of RAAS, up-regulation of renal sodium transporters and hypertension in the offspring.
authors.affiliation: Laboratory for Medical Research-LIM12, Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil pedrogoismd@usp.br.
authors.forename: Pedro Henrique França
authors.initials: PH
authors.lastname: Gois
authors.affiliation: Laboratory for Medical Research-LIM12, Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Daniele
authors.initials: D
authors.lastname: Canale
authors.affiliation: Laboratory for Medical Research-LIM12, Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Weverton Machado
authors.initials: WM
authors.lastname: Luchi
authors.affiliation: Laboratory for Medical Research-LIM12, Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Rildo Aparecido
authors.initials: RA
authors.lastname: Volpini
authors.affiliation: Laboratory of Experimental Air Pollution-LIM05, Department of Pathology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil.
authors.forename: Mariana Matera
authors.initials: MM
authors.lastname: Veras
authors.affiliation: Laboratory of Experimental Air Pollution-LIM05, Department of Pathology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil.
authors.forename: Natália de Souza Xavier
authors.initials: Nde S
authors.lastname: Costa
authors.affiliation: Laboratory for Medical Research-LIM12, Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Maria Heloisa Massola
authors.initials: MH
authors.lastname: Shimizu
authors.affiliation: Laboratory for Medical Research-LIM12, Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Antonio Carlos
authors.initials: AC
authors.lastname: Seguro
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D001693:Biological Transport, Active / Q000187:drug effects; D005260:Female; D006973:Hypertension / Q000139:chemically induced*; D023421:Models, Animal; D063065:Organophosphonates / Q000008:administration & dosage* / Q000009:adverse effects*; D011247:Pregnancy; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects; D012964:Sodium / Q000378:metabolism; D000068698:Tenofovir
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D000068698:Tenofovir; D012964:Sodium; D000225:Adenine
keywords: AIDS; HIV; hepatitis B; hypertension; pregnancy; tenofovir