Maternal caffeine administration leads to adverse effects on adult mice offspring
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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.
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.
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.
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.
KeywordsCaffeine Fetal programming Energy expenditure Cardiac hypertrophy Renin-angiotensin system Hypertension
The authors are grateful to Aline Penna and Thatiany Marinho for their technical assistance. This study was supported by the Brazilian agencies FAPERJ (Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro, www.faperj.br) grant number (E-26/111.456/2011); and CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnológico, www.cnpq.br) grant number (151781/2008 7); and CAPES (Coordenação de Aperfeiçoamento de Pessoa de Nível Superior).
Conflict of interest
The authors declare that there are no conflicts of interest.
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