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Physiol. Rev. 78: 583-686, 1998;
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PHYSIOLOGICAL REVIEWS   Vol. 78 No. 3 July 1998, pp. 583-686
Copyright ©1998 The American Physiological Society

Angiotensin, Thirst, and Sodium Appetite

J. T. FITZSIMONS

The Physiological Laboratory, Cambridge, United Kingdom

Fitzsimons, J. T. Angiotensin, Thirst, and Sodium Appetite. Physiol. Rev. 78: 583-686, 1998. --- Angiotensin (ANG) II is a powerful and phylogenetically widespread stimulus to thirst and sodium appetite. When it is injected directly into sensitive areas of the brain, it causes an immediate increase in water intake followed by a slower increase in NaCl intake. Drinking is vigorous, highly motivated, and rapidly completed. The amounts of water taken within 15 min or so of injection can exceed what the animal would spontaneously drink in the course of its normal activities over 24 h. The increase in NaCl intake is slower in onset, more persistent, and affected by experience. Increases in circulating ANG II have similar effects on drinking, although these may be partly obscured by accompanying rises in blood pressure. The circumventricular organs, median preoptic nucleus, and tissue surrounding the anteroventral third ventricle in the lamina terminalis (AV3V region) provide the neuroanatomic focus for thirst, sodium appetite, and cardiovascular control, making extensive connections with the hypothalamus, limbic system, and brain stem. The AV3V region is well provided with angiotensinergic nerve endings and angiotensin AT1 receptors, the receptor type responsible for acute responses to ANG II, and it responds vigorously to the dipsogenic action of ANG II. The nucleus tractus solitarius and other structures in the brain stem form part of a negative-feedback system for blood volume control, responding to baroreceptor and volume receptor information from the circulation and sending ascending noradrenergic and other projections to the AV3V region. The subfornical organ, organum vasculosum of the lamina terminalis and area postrema contain ANG II-sensitive receptors that allow circulating ANG II to interact with central nervous structures involved in hypovolemic thirst and sodium appetite and blood pressure control. Angiotensin peptides generated inside the blood-brain barrier may act as conventional neurotransmitters or, in view of the many instances of anatomic separation between sites of production and receptors, they may act as paracrine agents at a distance from their point of release. An attractive speculation is that some are responsible for long-term changes in neuronal organization, especially of sodium appetite. Anatomic mismatches between sites of production and receptors are less evident in limbic and brain stem structures responsible for body fluid homeostasis and blood pressure control. Limbic structures are rich in other neuroactive peptides, some of which have powerful effects on drinking, and they and many of the classical nonpeptide neurotransmitters may interact with ANG II to augment or inhibit drinking behavior. Because ANG II immunoreactivity and binding are so widely distributed in the central nervous system, brain ANG II is unlikely to have a role as circumscribed as that of circulating ANG II. Angiotensin peptides generated from brain precursors may also be involved in functions that have little immediate effect on body fluid homeostasis and blood pressure control, such as cell differentiation, regeneration and remodeling, or learning and memory. Analysis of the mechanisms of increased drinking caused by drugs and experimental procedures that activate the renal renin-angiotensin system, and clinical conditions in which renal renin secretion is increased, have provided evidence that endogenously released renal renin can generate enough circulating ANG II to stimulate drinking. But it is also certain that other mechanisms of thirst and sodium appetite still operate when the effects of circulating ANG II are blocked or absent, although it is not known whether this is also true for angiotensin peptides formed in the brain. Whether ANG II should be regarded primarily as a hormone released in hypovolemia helping to defend the blood volume, a neurotransmitter or paracrine agent with a privileged role in the neural pathways for thirst and sodium appetite of all kinds, a neural organizer especially in sodium appetite, or all of these, remains uncertain. ANG II-induced drinking behavior serves as a model of how other complex behaviors involving neural and peptide inputs might be organized.




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Identification of Angiotensin II Type 2 (AT2) Receptor Domains Mediating High-Affinity CGP 42112A Binding and Receptor Activation
J. Pharmacol. Exp. Ther., August 1, 2001; 298(2): 665 - 673.
[Abstract] [Full Text] [PDF]

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 Journal of Renin-Angiotensin-Aldosterone SystemHome page
J. Culman, J. Baulmann, A. Blume, and T. Unger
Review: The renin-angiotensin system in the brain: an update
Journal of Renin-Angiotensin-Aldosterone System, June 1, 2001; 2(2): 96 - 102.
[PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
Z. Xu, C. Glenda, L. Day, J. Yao, and M. G. Ross
Central angiotensin induction of fetal brain c-fos expression and swallowing activity
Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2001; 280(6): R1837 - R1843.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
D. M. Roesch, R. E. Blackburn-Munro, and J. G. Verbalis
Mineralocorticoid treatment attenuates activation of oxytocinergic and vasopressinergic neurons by icv ANG II
Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2001; 280(6): R1853 - R1864.
[Abstract] [Full Text] [PDF]

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 Journal of Renin-Angiotensin-Aldosterone SystemHome page
A. M Allen, M. E Giles, J. Lee, B. J Oldfield, F. A. Mendelsohn, and M. J McKinley
Review: AT1-receptors in the central nervous system
Journal of Renin-Angiotensin-Aldosterone System, March 1, 2001; 2(1_suppl): S95 - S101.
[PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
S. D. Stocker, E. M. Stricker, and A. F. Sved
Acute hypertension inhibits thirst stimulated by ANG II, hyperosmolality, or hypovolemia in rats
Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2001; 280(1): R214 - R224.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
Z. Xu, C. Glenda, L. Day, J. Yao, and M. G. Ross
Osmotic threshold and sensitivity for vasopressin release and Fos expression by hypertonic NaCl in ovine fetus
Am J Physiol Endocrinol Metab, December 1, 2000; 279(6): E1207 - E1215.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
M. L. Mathai, T. Hubschle, and M. J. McKinley
Central angiotensin receptor blockade impairs thermolytic and dipsogenic responses to heat exposure in rats
Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2000; 279(5): R1821 - R1826.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
E. Watanabe, A. Fujikawa, H. Matsunaga, Y. Yasoshima, N. Sako, T. Yamamoto, C. Saegusa, and M. Noda
Nav2/NaG Channel Is Involved in Control of Salt-Intake Behavior in the CNS
J. Neurosci., October 15, 2000; 20(20): 7743 - 7751.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
Y. Takei and T. Tsuchida
Role of the renin-angiotensin system in drinking of seawater-adapted eels Anguilla japonica: a reevaluation
Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2000; 279(3): R1105 - R1111.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
A. M. Schreihofer, E. M. Stricker, and A. F. Sved
Nucleus of the solitary tract lesions enhance drinking, but not vasopressin release, induced by angiotensin
Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2000; 279(1): R239 - R247.
[Abstract] [Full Text] [PDF]

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 J. Neurophysiol.Home page
O. V. B. U. Halbach, T. Walther, M. Bader, and D. Albrecht
Interaction Between Mas and the Angiotensin AT1 Receptor in the Amygdala
J Neurophysiol, April 1, 2000; 83(4): 2012 - 2021.
[Abstract] [Full Text] [PDF]

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 PhysiologyHome page
E. Simon
Interface Properties of Circumventricular Organs in Salt and Fluid Balance
Physiology, April 1, 2000; 15(2): 61 - 67.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
A. Hamada, K. Inenaga, S. Nakamura, M. Terashita, and H. Yamashita
Disorder of salivary secretion in inbred polydipsic mouse
Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2000; 278(4): R817 - R823.
[Abstract] [Full Text] [PDF]

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 J. Exp. Biol.Home page
A Delorenzi, B Dimant, L Frenkel, V. Nahmod, D. Nassel, and H Maldonado
High environmental salinity induces memory enhancement and increases levels of brain angiotensin-like peptides in the crab Chasmagnathus granulatus
J. Exp. Biol., January 11, 2000; 203(22): 3369 - 3379.
[Abstract] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
C. E. Wood and H. Tong
Central nervous system regulation of reflex responses to hypotension during fetal life
Am J Physiol Regulatory Integrative Comp Physiol, December 1, 1999; 277(6): R1541 - R1552.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
P. Sinnayah, P. Burns, J. D. Wade, R. S. Weisinger, and M. J. McKinley
Water Drinking in Rats Resulting from Intravenous Relaxin and Its Modification by Other Dipsogenic Factors
Endocrinology, November 1, 1999; 140(11): 5082 - 5086.
[Abstract] [Full Text]

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 Am. J. Physiol. Renal Physiol.Home page
P. L. Sinn, X. Zhang, and C. D. Sigmund
JG cell expression and partial regulation of a human renin genomic transgene driven by a minimal renin promoter
Am J Physiol Renal Physiol, October 1, 1999; 277(4): F634 - F642.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
T. N. Thrasher, C. R. Keenan, and D. J. Ramsay
Cardiovascular afferent signals and drinking in response to hypotension in dogs
Am J Physiol Regulatory Integrative Comp Physiol, September 1, 1999; 277(3): R795 - R801.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
J. W. Wright, L. Stubley, E. S. Pederson, E. A. Kramar, J. M. Hanesworth, and J. W. Harding
Contributions of the Brain Angiotensin IV-AT4 Receptor Subtype System to Spatial Learning
J. Neurosci., May 15, 1999; 19(10): 3952 - 3961.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
N. E. Rowland and K. R. Morian
Roles of aldosterone and angiotensin in maturation of sodium appetite in furosemide-treated rats
Am J Physiol Regulatory Integrative Comp Physiol, May 1, 1999; 276(5): R1453 - R1460.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
D. Denton, R. Shade, F. Zamarippa, G. Egan, J. Blair-West, M. McKinley, J. Lancaster, and P. Fox
Neuroimaging of genesis and satiation of thirst and an interoceptor-driven theory of origins of primary consciousness
PNAS, April 27, 1999; 96(9): 5304 - 5309.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
L. F. Franchini and L. Vivas
Distribution of Fos immunoreactivity in rat brain after sodium consumption induced by peritoneal dialysis
Am J Physiol Regulatory Integrative Comp Physiol, April 1, 1999; 276(4): R1180 - R1187.
[Abstract] [Full Text] [PDF]


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