Enhanced central response to dehydration in mice lacking angiotensin AT(1a) receptors

The objective was to determine the central nervous system (CNS) responses t o dehydration (c-Fos and vasopressin mRNA) in mice lacking the ANG AT(1a) r eceptor [ANG AT(1a) knockout (KO)]. Control and AT(1a) KO mice were dehydra ted for 24 or 48 h. Baseline plasma vasopressin (VP) was not different betw een the groups; however, the response to dehydration was attenuated in AT(1 a) KO (24 +/- 11 vs. 10.6 +/- 2.7 pg/ml). Dehydration produced similar incr eases 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 parave ntricular nucleus (PVN), c-Fos-positive neurons (57.4 +/- 10.7 vs. 98.4 +/- 7.4 c-Fos cells/PVN, control vs. AT(1a) KO) and VP mu mRNA levels (1.0 +/- 0.1 vs. 1.4 +/- 0.1 Ci, control vs. AT(1a) KO) were increased with greater responses in AT(1a) KO. A comparison of 1- to 2-day water deprivation show ed that plasma VP, brain c-Fos, and VP mRNA returned toward control on day 2, although plasma osmolality remained high. Data demonstrate that AT(1a) K O mice show a dichotomous response to dehydration, reduced for plasma VP an d enhanced for PVN c-Fos protein and VP mRNA. The results illustrate the im portance of ANG AT(1a) receptors in the regulation of osmotic and endocrine balance.