Physiological regulation of brain angiotensin receptor mRNA in AT1a deficient mice.
Experiments were performed to study the physiological regulation of angiotensin (Ang) AT1b receptors using Ang AT1a knockout mice (AT1aKO). Ang AT1b mRNA was analyzed in forebrain, hypothalamus, and brainstem using in situ hybridization (ISH) under baseline and water-restricted conditions. Plasma was analyzed for osmolality, vasopressin, and corticosterone. Dehydration (24 h) increased osmolality and corticosterone and decreased body weight with no difference between groups. Plasma vasopressin was not different between the groups and was not stimulated by dehydration. Under water ad libitum conditions, there were no differences in AT1b mRNA expression in medial periventricular, anterior third ventricle (AV3V), and subfornical organ (SFO) between controls and AT1aKO. In contrast, there was higher expression in the dorsal motor nucleus of the vagus (DMV) of AT1aKO vs. Controls (0.6 +/- 0.1 vs. 0.9 +/- 0.1 microCi/g, Control vs. AT1aKO in water ad libitum group). Dehydration increased AT1b expression in SFO in AT1aKO, but not in controls (0.6 +/- 0.07 vs. 0.9 +/- 0.06 microCi/g; water ad libitum vs. dehydrated). Emulsion autoradiography documents the detailed pattern of AT1b expression in brainstem of controls and AT1aKO. There was labeling in DMV, locus coeruleus, inferior olive, lateral reticular nucleus, and caudalis spinal trigemius. In conclusion, deletion of AT1a receptors produces a compensatory increase in AT1b receptor mRNA expression in brainstem, but not in hypothalamus or rostral forebrain. In addition, AT1aKO mice showed an enhanced response to dehydration in terms of AT1b mRNA expression in SFO.
Rocha
Maria José Alves
MJ
Department of Morphology, Stomatology and Physiology, University of São Paulo, School of Dentistry of Ribeirão Preto, Avenue Café, 14040-904, Ribeirão Preto, SP, Brazil.
Chen
Yanfang
Y
Oliveira
Gabriela Ravanelli
GR
Morris
Mariana
M
D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D005786:Gene Expression Regulation; D017403:In Situ Hybridization / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay / Q000379:methods; D044140:Receptor, Angiotensin, Type 1 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D014667:Vasopressins / Q000097:blood; D014868:Water Deprivation / Q000502:physiology
D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D014667:Vasopressins; D003345:Corticosterone