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1 Department of Pharmacology and Toxicology, Wright State University School of Medicine, Dayton, Ohio 45401; 2 Department of Medicine, Duke University, Winston-Salem; and Veterans Affairs Medical Center, Durham, North Carolina 27705
The objective was to determine the central nervous system (CNS) responses to dehydration (c-Fos and vasopressin mRNA) in mice lacking the ANG AT1a receptor [ANG AT1a knockout (KO)]. Control and AT1a KO mice were dehydrated for 24 or 48 h. Baseline plasma vasopressin (VP) was not different between the groups; however, the response to dehydration was attenuated in AT1a KO (24 ± 11 vs. 10.6 ± 2.7 pg/ml). Dehydration produced similar increases in plasma osmolality and depletion of posterior pituitary VP content. Neuronal activation was observed as increases in c-Fos protein and VP mRNA. The supraoptic responses were not different between groups. In the paraventricular nucleus (PVN), c-Fos-positive neurons (57.4 ± 10.7 vs. 98.4 ± 7.4 c-Fos cells/PVN, control vs. AT1a KO) and VP mRNA levels (1.0 ± 0.1 vs. 1.4 ± 0.1 µCi, control vs. AT1a KO) were increased with greater responses in AT1a KO. A comparison of 1- to 2-day water deprivation showed that plasma VP, brain c-Fos, and VP mRNA returned toward control on day 2, although plasma osmolality remained high. Data demonstrate that AT1a KO mice show a dichotomous response to dehydration, reduced for plasma VP and enhanced for PVN c-Fos protein and VP mRNA. The results illustrate the importance of ANG AT1a receptors in the regulation of osmotic and endocrine balance.
central nervous system; hypothalamus; water balance; blood pressure; molecular genetics; knockout models; paraventricular nucleus
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