Sexual Dimorphism in the Expression of Cardiac and Hippocampal Renin-Angiotensin and Kallikrein–Kinin Systems in Offspring from Mice Exposed to Alcohol during Gestation

Abstract

Prenatal alcohol exposure (PAE) impairs fetal development. Alcohol consumption was shown to modulate the renin–angiotensin system (RAS). This study aimed to analyze the effects of PAE on the expression of the renin–angiotensin system (RAS) and kallikrein–kinin system (KKS) peptide systems in the hippocampus and heart of mice of both sexes. C57Bl/6 mice were exposed to alcohol during pregnancy at a concentration of 10% (v/v). On postnatal day 45 (PN45), mouse hippocampi and left ventricles (LV) were collected and processed for messenger RNA (mRNA) expression of components of the RAS and KKS. In PAE animals, more pronounced expression of AT1 and ACE mRNAs in males and a restored AT2 mRNA expression in females were observed in both tissues. In LV, increased AT2, ACE2, and B2 mRNA expressions were also observed in PAE females. Furthermore, high levels of H2O2 were observed in males from the PAE group in both tissues. Taken together, our results suggest that modulation of the expression of these peptidergic systems in PAE females may make them less susceptible to the effects of alcohol.

Paternal preconception alcohol consumption increased Angiotensin II‐mediated vasoconstriction in male offspring cerebral arteries via oxidative stress‐AT1R pathway

“…10 The stronger MCA contraction in the offspring exposed to paternal preconception alcohol consumption was mainly via increased activities and expression of AT1R, especially its subunit1α rather than (ACE) and decreased expressions of AT2R in the offspring renal arteries. 21,37 Alcohol intake could directly increase plasma AngII concentrations in rats. 20 This study firstly demonstrated that paternal preconception alcohol changed the activities of RAS elements in the Ion channels, such as calcium channels and potassium channels, play an important role in AngII-mediated constriction in MCA.…”

“…Meanwhile, the present study uncovered higher circulating AngII concentrations in the alcohol offspring, which might contribute to the potentiated vascular contraction and indicated the activation of RAS. Maternal alcohol consumption during pregnancy increased expressions of AT1αR and angiotensin‐converting enzyme (ACE) and decreased expressions of AT2R in the offspring renal arteries 21,37 . Alcohol intake could directly increase plasma AngII concentrations in rats 20 .…”

“…Maternal alcohol consumption during pregnancy increased expressions of AT1αR and angiotensin‐converting enzyme (ACE) and decreased expressions of AT2R in the offspring renal arteries. 21 , 37 Alcohol intake could directly increase plasma AngII concentrations in rats. 20 This study firstly demonstrated that paternal preconception alcohol changed the activities of RAS elements in the male offspring cerebral arteries.…”