AccScience Publishing / AN / Volume 2 / Issue 2 / DOI: 10.36922/an.393
Cite this article
Journal Browser
Volume | Year
News and Announcements
View All

AT1 receptor role in the hypothalamic and renal function interaction

Celia Ruberto1 Victoria Belén Occhieppo2 Claudia Bregonzio2* Gustavo Baiardi1
Show Less
1 Laboratory of Neuropharmacology, IIBYT-CONICET, National University of Córdoba, Córdoba, Argentina
2 Experimental Pharmacology Institute of Córdoba, IFEC-CONICET, Department of Pharmacology “Otto Orsingher,” Faculty of Chemical Sciences, National University of Córdoba, Córdoba, Argentina
Advanced Neurology 2023, 2(2), 393
Submitted: 22 March 2023 | Accepted: 2 May 2023 | Published: 24 May 2023
© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( )

Angiotensin II (ANG II) is involved in renal sodium homeostasis under normal and pathological conditions in close relation with the sympathetic nervous system. Vasopressin, a hormone that modulates renal sodium and water reabsorption, is synthesized and released in the supraoptic and paraventricular nucleus under the influence of ANG II. We hypothesized that brain ANG II (AT1) receptors regulate renal sodium and water reabsorption and excretion through the sympathetic nervous system. In this study, male Wistar rats with renal denervation/sham were fed a hypersodic (4%) or normal (0.4%) diet and evaluated during 5 days in metabolic cages. On day 5, they were injected in the lateral ventricle with an AT1 receptor antagonist, losartan, and sacrificed 12 h later; blood samples and brains were obtained for evaluation. The urine was collected daily. The neuronal activation was analyzed in the nucleus of the supraoptic, paraventricular, subfornical, and organum vasculosum of the lamina terminalis. Activation of vasopressin neurons was evaluated in the supraoptic nucleus. Depending on renal nerve integrity, the hypersodic diet or losartan administration differentially affected neuronal activation. In sham animals, losartan prevented the stimulatory effects induced by the hypersodic diet in water intake and the neuronal activation in vasopressin-positive neurons. Renal denervation modified the effect of the hypersodic diet on water intake, urinary volume, and creatinine excretion, and losartan administration was able to prevent these alterations. Food intake was similar in all groups. Our results suggest that brain AT1 receptors regulate renal sodium and water reabsorption through the sympathetic nervous system in close interaction with vasopressin.

Renal denervation
Sodium intake
Agencia Nacional de Promoción Científica y Tecnológica
  1. Blair-West JR, Carey KD, Denton DA, et al., 1998, Evidence that brain angiotensin II is involved in both thirst and sodium appetite in baboons. Am J Physiol, 275: R1639– R1646.


  1. Fitzsimons JT, 1998, Angiotensin, thirst, and sodium appetite. Physiol Rev, 78: 583–686.


  1. Alova LG, Stancheva SL, Matsoukas J, et al., 1999, Effects of peptide and non-peptide antagonists of angiotensin II receptors on drinking behavior in rats. J Physiol Paris, 93: 219–224.


  1. De Gasparo M, Catt KJ, Inagami T, et al., 2000, International union of pharmacology. XXIII. The angiotensin II receptors. Pharmacol Rev, 52: 415–472.


  1. Saavedra JM, Ando H, Armando I, et al., 2005, Anti-stress and anti-anxiety effects of centrally acting angiotensin II AT1 receptor antagonists. Regul Pept, 128: 227–238.


  1. DiBona GF, 2000, Nervous kidney. Interaction between renal sympathetic nerves and the renin-angiotensin system in the control of renal function. Hypertension, 36: 1083–1088.


  1. Johns EJ, Kopp UC, DiBona GF, 2011, Neural control of renal function. Compr Physiol, 1: 731–767.


  1. DiBona, GF, 2005, Physiology in perspective: The Wisdom of the Body. Neural control of the kidney. Am J Physiol Regul Integr Comp Physiol, 289: R633–R641.


  1. Pontes RB, Girardi AC, Nishi EE, et al., 2015, Crosstalk between the renal sympathetic nerve and intrarenal angiotensin II modulates proximal tubular sodium reabsorption. Exp Physiol, 100: 502–506.


  1. Johnson AK, Zardetto-Smith AM, Edwards GL, 1992, Integrative mechanisms and the maintenance of cardiovascular and body fluid homeostasis: The central processing of sensory input derived from the circumventricular organs of the lamina terminalis. Prog Brain Res, 91: 381–393.


  1. Brownstein MJ, Russell JT, Gainer H, 1980, Synthesis, transport, and release of posterior pituitary hormones. Science, 207: 373–378.


  1. Sakai K, Agassandian K, Morimoto S, et al., 2007, Local production of angiotensin II in the subfornical organ causes elevated drinking. J Clin Invest, 117: 1088–1095.


  1. Simpson JB, Routtenberg A, 1973, Subfornical organ: Site of drinking elicitation by angiotensin II. Science, 181: 1172–1175.


  1. Vivas L, Chiaraviglio E, Carrer HF, 1990, Rat organum vasculosum laminae terminalis in vitro: Responses to changes in sodium concentration. Brain Res, 519: 294–300.


  1. Kopp UC, Jones SY, DiBona GF, 2008, Afferent renal denervation impairs baroreflex control of efferent renal sympathetic nerve activity. Am J Physiol Regul Integr Comp Physiol, 295: R1882–R1890.


  1. Mendelsohn FA, Allen AM, Chai SY, et al., 1990, The brain angiotensin system: Insights from mapping its components. Trends Endocrinol Metab, 1: 189–198.


  1. Bourque CW, 2008, Central mechanisms of osmosensation and systemic osmoregulation. Nat Rev Neurosci, 9: 519–531.


  1. Stocker SD, Simmons JR, Stornetta RL, et al., 2006, Water deprivation activates a glutamatergic projection from the hypothalamic paraventricular nucleus to the rostral ventrolateral medulla. J Comp Neurol, 494: 673–685.


  1. Shi P, Stocker SD, Toney GM, 2007, Organum vasculosum laminae terminalis contributes to increased sympathetic nerve activity induced by central hyperosmolality. Am J Physiol Regul Integr Comp Physiol, 293: R2279–R2289.


  1. McKinley MJ, Albiston AL, Allen AM, et al., 2003, The brain renin-angiotensin system: Location and physiological roles. Int J Biochem Cell Biol, 35: 901–918.


  1. Llorens-Cortes C, Mendelsohn FA, 2002, Organisation and functional role of the brain angiotensin system. J Renin Angiotensin Aldosterone Syst, 3(Suppl 1): S39–S48.


  1. Ye S, Zhong H, Duong VN, et al., 2002, Losartan reduces central and peripheral sympathetic nerve activity in a rat model of neurogenic hypertension. Hypertension, 39: 1101– 1106.


  1. McKinley MJ, Evered M, Mathai M., et al., 1994, Effects of central losartan on plasma renin and centrally mediated natriuresis. Kidney Int, 46: 1479–1482.


  1. Mathai M, Evered MD, McKinley MJ, 1997, Intracerebroventricular losartan inhibits postprandial drinking in sheep. Am J Physiol, 272(4 Pt 2): R1055–R1059.


  1. Mathai ML, Evered MD, McKinley MJ, 1998, Central losartan blocks natriuretic, vasopressin, and pressor responses to central hypertonic NaCl in sheep. Am J Physiol, 275: R548–R554.


  1. Paxinos G, Watson RW, 2009, The Rat Brain in Stereotaxic Coordinates. Oxford: Elsevier. p128.


  1. King AJ, Osborn JW, Fink GD, 2007, Splanchnic circulation is a critical neural target in angiotensin II salt hypertension in rats. Hypertension, 50: 547–556.


  1. Foss JD, Fink GD, Osborn JW, 2013, Reversal of genetic salt-sensitive hypertension by targeted sympathetic ablation. Hypertension, 61: 806–811.


  1. Hong MN, Li XD, Chen DR, et al., 2016, Renal denervation attenuates aldosterone expression and associated cardiovascular pathophysiology in angiotensin II-induced hypertension. Oncotarget, 7: 67828–67840.


  1. Li, JD, Cheng AY, Huo YL, et al., 2016, Bilateral renal denervation ameliorates isoproterenol-induced heart failure through downregulation of the brain renin-angiotensin system and inflammation in rat. Oxid Med Cell Longev, 2016: 3562634.


  1. Fitts DA, Zierath DK, Wilkins EE, et al., 2005, Losartan blocks drinking and cFos expression induced by central ornithine vasotocin in rats. Physiol Behav, 86: 573–577.


  1. Lopez LH, Caif F, Garcia S, et al., 2012, Anxiolytic-like effect of losartan injected into amygdala of the acutely stressed rats. Pharmacol Rep, 64: 54–63.


  1. Franchini LF, Johnson AK, de Olmos J, et al., 2002, Sodium appetite and Fos activation in serotonergic neurons. Am J Physiol Regul Integr Comp Physiol, 282: R235–R243.


  1. Franchini LF, Vivas L, 1999, Distribution of Fos immunoreactivity in rat brain after sodium consumption induced by peritoneal dialysis. Am J Physiol, 276: R1180– R1187.


  1. Mendelsohn FA, Quirion R, Saavedra JM, et al., 1984, Autoradiographic localization of angiotensin II receptors in rat brain. Proc Natl Acad Sci U S A, 81: 1575–1579.


  1. Saavedra JM, 1992, Brain and pituitary angiotensin. Endocr Rev, 13: 329–380.


  1. Phillips MI, Sumners C, 1998, Angiotensin II in central nervous system physiology. Regul Pept, 78: 1–11.


  1. Zhuo J, Moeller I, Jenkins T, et al., 1998, Mapping tissue angiotensin-converting enzyme and angiotensin AT1, AT2 and AT4 receptors. J Hypertens, 16(12 Pt 2): 2027–2037.


  1. Vivas L, Godino A, Dalmasso C, et al., 2014, Neurochemical Circuits Subserving Fluid Balance and Baroreflex: A Role for Serotonin, Oxytocin, and Gonadal Steroids. Boca Raton, FL: CRC Press/Taylor & Francis.


  1. McKinley MJ, McBurnie MI, Mathai ML, 2001, Neural mechanisms subserving central angiotensinergic influences on plasma renin in sheep. Hypertension, 37: 1375–1381.


  1. Unger T, Horst PJ, Bauer M, et al., 1989, Natriuretic action of central angiotensin II in conscious rats. Brain Res, 486: 33–38.


  1. Sofroniew MV, 1983, Morphology of vasopressin and oxytocin neurones and their central and vascular projections. Prog Brain Res, 60: 101–114.


  1. Stern JE, 2015, Neuroendocrine-autonomic integration in the paraventricular nucleus: Novel roles for dendritically released neuropeptides. J Neuroendocrinol, 27: 487–497.


  1. Brown CH, Bains JS, Ludwig M, et al., 2013, Physiological regulation of magnocellular neurosecretory cell activity: Integration of intrinsic, local and afferent mechanisms. J Neuroendocrinol, 25: 678–710.


  1. Antunes-Rodrigues J, de Castro M, Elias LL, et al., 2004, Neuroendocrine control of body fluid metabolism. Physiol Rev, 84: 169–208.


  1. Unger T, Badoer E, Gareis C, et al., 1990, Atrial natriuretic peptide (ANP) as a neuropeptide: Interaction with angiotensin. Br J Clin Pharmacol, 30: 83S–88S.


  1. Cao W, Li A, Wang L, et al., 2015, A salt-induced reno-cerebral reflex activates renin-angiotensin systems and promotes CKD progression. J Am Soc Nephrol, 26: 1619–1633.


  1. Daniels D, Mietlicki EG, Nowak EL, et al., 2009, Angiotensin II stimulates water and NaCl intake through separate cell signalling pathways in rats. Exp Physiol, 94: 130–137.


  1. Jacob F, Ariza P, Osborn JW, 2003, Renal denervation chronically lowers arterial pressure independent of dietary sodium intake in normal rats. Am J Physiol Heart Circ Physiol, 284: H2302–H2310.


  1. Nishi EE, Bergamaschi CT, Campos RR, 2015, The crosstalk between the kidney and the central nervous system: The role of renal nerves in blood pressure regulation. Exp Physiol, 100: 479–484.


  1. Gasparini S, Melo MR, Nascimento PA, et al., 2019, Interaction of central angiotensin II and aldosterone on sodium intake and blood pressure. Brain Res, 1720: 146299.
Conflict of interest
The authors have no conflicts of interest to report nor any involvements to disclose, financial, or otherwise.
Back to top
Advanced Neurology, Electronic ISSN: 2810-9619 Published by AccScience Publishing