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(Hypertension. 1999;33:482-486.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Neuroendocrine Effects of Dehydration in Mice Lacking the Angiotensin AT1a Receptor

Mariana Morris; Ping Li; Michael F. Callahan; Michael I. Oliverio; Thomas M. Coffman; Susan M. Bosch; Debra I. Diz

From the Department of Pharmacology and Toxicology (M.M.), Wright State University School of Medicine, Dayton, OH; the Hypertension Center and Department of Physiology and Pharmacology (M.F.C., S.M.B., D.I.D.), Wake Forest University Medical Center, Winston-Salem, NC; and the Department of Medicine (M.I.O., T.M.C.), Duke University and VA Medical Center, Durham, NC.

Correspondence to Mariana Morris, PhD, Department of Pharmacology and Toxicology, Box 927, Wright State University School of Medicine, Dayton, OH 45401. E-mail mmorris{at}wright.edu

Abstract—Angiotensin (Ang) type 1a (AT1a) receptors are critical in the control of blood pressure and water balance. Experiments were performed to determine the influence of dehydration on brain Ang receptors and plasma vasopressin (VP) in mice lacking this receptor. Control or AT1a knockout (AT1aKO) male mice were give water ad libitum or deprived of water for 48 hours. Animals were anesthetized with halothane, blood samples were collected by heart puncture, and brains were processed for Ang-receptor autoradiography with ¹²⁵I-sarthran (0.4 nmol/L). Dehydration produced an increase in AT1 receptors in the paraventricular nucleus (PVN) and anterior pituitary (AP) in control mice (PVN: 70±16 versus 146±10 fmol/mg protein; AP: 41±7 versus 86±15 fmol/mg protein). No changes were noted in the median preoptic nucleus. The majority of the brain receptors were of the AT1 subtype. There was little or no specific Ang binding in AT1aKO mice and no effect of dehydration. Plasma VP levels were elevated in the halothane-anesthetized animals (>200 pg/mL) with no significant effect of dehydration. A separate experiment was performed with decapitated mice anesthetized with pentobarbital. Dehydration increased plasma VP in control mice, from 3.3±0.6 to 13.3±4.7 pg/mL, whereas no change was noted in the AT1aKO mice, 5.1±0.3 versus 6.1±0.7 pg/mL (water versus dehydration). These results demonstrate a differential response to dehydration in mice lacking AT1a receptors. There was no evidence for AT1 receptors of any subtype in the brain regions examined and no effect of dehydration on VP secretion or brain Ang receptors.

Key Words: central nervous system • hypothalamus • vasopressin • water balance • blood pressure

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