title: Maternal caffeine administration leads to adverse effects on adult mice offspring.
abstract: OBJECTIVE
  This study aimed to evaluate the role of caffeine chronic administration during gestation of C57BL/6 mice on cardiac remodeling and the expression of components of the renin-angiotensin system (RAS) in male offspring as adults.
  
  
  METHODS
  Pregnant C57BL/6 female mice were divided into two groups (n = 10): Control group (C), dams were injected with the vehicle only (saline 0.9% NaCl); Caffeine group (CF), dams received daily a subcutaneous injection of 20 mg/kg of caffeine/day (1 mg/mL saline). Pups had free access to standard chow since weaning to 3 months of age, when they were killed.
  
  
  RESULTS
  CF group showed increased energy expenditure (+7%) with consequent reduction in body mass (BM) gain (-18%), increased blood pressure (+48%), and higher heart rate (+10%) than C group. The ratio between LV mass/BM was greater (+10%), with bigger cardiomyocytes (+40%), and reduced vascularization (-25%) in CF group than in C group. In the LV, the expression of angiotensin-converting enzyme (+30%), Angiotensin II (AngII) (+60%), AngII receptor (ATR)-1 (+77%) were higher, and the expression of ATR-2 was lower (-46%; P < 0.05) in CF group than in C group. In the kidney, the expressions of renin (+128%) and ATR-1 (+88%) were higher in CF group than in C group.
  
  
  CONCLUSIONS
  Chronic administration of caffeine to pregnant dams led to persistent activation of local RAS in the kidney and heart of the offspring, which, in turn, leads to high BP and adverse cardiac remodeling. These findings highlight the urge to encourage pregnant women to avoid food or medicines containing caffeine.
authors.affiliation: Laboratory of Morphometry, Metabolism and Cardiovascular Diseases, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Av 28 de Setembro, 87, fundos, FCM, terreo, Rio de Janeiro, 20551-030, Brazil.
authors.forename: Diana F
authors.initials: DF
authors.lastname: Serapiao-Moraes
authors.forename: Vanessa
authors.initials: V
authors.lastname: Souza-Mello
authors.forename: Marcia B
authors.initials: MB
authors.lastname: Aguila
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Mandarim-de-Lacerda
authors.forename: Tatiane S
authors.initials: TS
authors.lastname: Faria
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002110:Caffeine / Q000008:administration & dosage* / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000196:embryology*; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000196:embryology; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects
chemical_list: D000804:Angiotensin II; D002110:Caffeine; D012083:Renin