Enhanced central response to dehydration in mice lacking angiotensin AT(1a) receptors.
The objective was to determine the central nervous system (CNS) responses to dehydration (c-Fos and vasopressin mRNA) in mice lacking the ANG AT(1a) receptor [ANG AT(1a) knockout (KO)]. Control and AT(1a) 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 AT(1a) 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. AT(1a) KO) and VP mRNA levels (1.0 +/- 0.1 vs. 1.4 +/- 0.1 microCi, control vs. AT(1a) KO) were increased with greater responses in AT(1a) 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 AT(1a) 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 AT(1a) receptors in the regulation of osmotic and endocrine balance.
Department of Pharmacology and Toxicology, Box 927, Wright State University School of Medicine, Dayton, OH 45401, USA. mariana.morris@wright.edu
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D000818:Animals; D003433:Crosses, Genetic; D003681:Dehydration / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D016762:Genes, fos; D005838:Genotype; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology*; D010902:Pituitary Gland / Q000502:physiology / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014667:Vasopressins / Q000032:analysis / Q000235:genetics
D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D014667:Vasopressins