Research ReportPrenatal water deprivation alters brain angiotensin system and dipsogenic changes in the offspring

Objective: Central renin-angiotensin system (RAS) plays an important role in regulating body fluid balance. The present study determined the effect of maternal dehydration on brain expression levels of angiotensinogen, angiotensin II receptor subtypes, and dipsogenic responses in offspring. Methods: Pregnant rats were deprived of water during late gestation. Expressions of brain angiotensinogen, angiotensin II receptors, and dipsogenic responses were determined. Results: Maternal water deprivation significantly decreased fetal body and brain weight, and body and tail length. Fetal plasma sodium, osmolality, and hematocrit were increased. Both AT1R and AT2R protein abundance was significantly increased in the fetal brain, associating with increased mRNA levels of AT1aR and AT2R. Additionally, angiotensinogen mRNA was increased. In adult offspring, prenatal dehydration resulted in significant increases in AT1R protein and AT1aR mRNA, as well as angiotensinogen mRNA in the forebrain in both males and females. In contrast, AT2R mRNA and protein were increased only in males. Prenatal dehydration resulted in a significant increase in intracerebroventricular angiotensin II-induced water intake in male, but not female, offspring. Conclusion: The results provided new information that antenatal water deprivation induces a reprogramming of brain RAS and Ang II receptor expression patterns and alters the central Ang II-mediated dipsogenic response in offspring in a sex-dependent manner.

Research Highlights► Fetal brain mRNA and protein of AT1R and AT2R, and angiotensinogen mRNA, were elevated. ► AT2R increase in the offspring brain was in the male, not female offspring. ► Ang II increased drinking in male not female offspring exposed to prenatal dehydration. ► Prenatal dehydration affected development of the brain RAS.