[Show abstract][Hide abstract] ABSTRACT: 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.
Pregnant rats were deprived of water during late gestation. Expressions of brain angiotensinogen, angiotensin II receptors, and dipsogenic responses were determined.
Maternal water deprivation significantly decreased fetal body and brain weight, and body and tail length. Fetal plasma sodium, osmolality, and hematocrit were increased. Both AT(1)R and AT(2)R protein abundance was significantly increased in the fetal brain, associating with increased mRNA levels of AT(1a)R and AT(2)R. Additionally, angiotensinogen mRNA was increased. In adult offspring, prenatal dehydration resulted in significant increases in AT(1)R protein and AT(1a)R mRNA, as well as angiotensinogen mRNA in the forebrain in both males and females. In contrast, AT(2)R 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.
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.
[Show abstract][Hide abstract] ABSTRACT: Hypoxia in pregnancy may induce fetal growth restriction and cause functional abnormalities during development. The present study determined the long-term influence of hypoxia in fetal life on dipsogenic behavior linked to central angiotensin (Ang) network in the offspring rats. Fetal blood pO(2) and body weight were decreased by hypoxia during pregnancy, followed by a postnatal "catch-up" growth. Subcutaneous hypertonic saline or intracerebroventricular Ang II significantly increased salt intake in the offspring prenatally exposed to hypoxia, while water intake was the same between the two groups. Ang II-induced c-fos expression was detected in the paraventricular nuclei, median preoptic nuclei, supraoptic nuclei, and subfornical organ in the brain, in association with reduced forebrain AT(2) receptor protein abundance in the offspring prenatally exposed to hypoxia. Levels of central AT(1) receptor protein were not changed between the two groups. Hypoxia during pregnancy could be linked to developmental problems related to behavioral dysfunctions in body fluid regulations in later life, in association with the change in central angiotensin II-mediated neural activation and expression of the Ang II receptor in the brain.