Brain Angiotensinergic Regulation of the Immune System: Implications for Cardiovascular and Neuroendocrine Responses

Author(s): Michele Iovino, Tullio Messana, Giovanni De Pergola, Emanuela Iovino, Edoardo Guastamacchia, Brunella Licchelli, Aldo Vanacore, Vito A. Giagulli, Vincenzo Triggiani*

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets
(Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders)

Volume 20 , Issue 1 , 2020

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Graphical Abstract:


Objective: The Renin-Angiotensin-Aldosterone System (RAAS) plays a major role in the regulation of cardiovascular functions, water and electrolytic balance, and hormonal responses. We perform a review of the literature, aiming at providing the current concepts regarding the angiotensin interaction with the immune system in the brain and the related implications for cardiovascular and neuroendocrine responses.

Methods: Appropriate keywords and MeSH terms were identified and searched in Pubmed. Finally, references of original articles and reviews were examined.

Results: Angiotensin II (ANG II), beside stimulating aldosterone, vasopressin and CRH-ACTH release, sodium and water retention, thirst, and sympathetic nerve activity, exerts its effects on the immune system via the Angiotensin Type 1 Receptor (AT 1R) that is located in the brain, pituitary, adrenal gland, and kidney. Several actions are triggered by the binding of circulating ANG II to AT 1R into the circumventricular organs that lack the Blood-Brain-Barrier (BBB). Furthermore, the BBB becomes permeable during chronic hypertension thereby ANG II may also access brain nuclei controlling cardiovascular functions. Subfornical organ, organum vasculosum lamina terminalis, area postrema, paraventricular nucleus, septal nuclei, amygdala, nucleus of the solitary tract and retroventral lateral medulla oblongata are the brain structures that mediate the actions of ANG II since they are provided with a high concentration of AT 1R. ANG II induces also T-lymphocyte activation and vascular infiltration of leukocytes and, moreover, oxidative stress stimulating inflammatory responses via inhibition of endothelial progenitor cells and stimulation of inflammatory and microglial cells facilitating the development of hypertension.

Conclusion: Besides the well-known mechanisms by which RAAS activation can lead to the development of hypertension, the interactions between ANG II and the immune system at the brain level can play a significant role.

Keywords: Angiotensin, angiotensin receptors, immune system, oxidative stress, circumventricular organs, cardiovascular brain nuclei, autonomic and neuroendocrine outputs.

de Gasparo, M.; Catt, K.J.; Inagami, T.; Wright, J.W.; Unger, T. International union of pharmacology. XXIII. The angiotensin II receptors. Pharmacol. Rev., 2000, 52(3), 415-472.
[PMID: 10977869]
Singh, K.D.; Karnik, S.S. Angiotensin receptors: structure, function, signaling and clinical applications J. Cell. Signal., 2016, 1, 111.
Zubcevic, J.; Santisteban, M.M.; Pitts, T.; Barkey, D.M.; Perez, P.D.; Bolser, D.C.; Febo, M.; Raizada, M.K. Functional neural-bone marrow pathway: implications in hypertension and cardiovascular disease. Hypertension, 2014, 63, 129-139.
Sayeski, P.P.; Bernstein, K.E. Signal transduction mechanisms of the angiotensin II type AT(1)-receptor: looking beyond the heterotrimeric G protein paradigm. J. Renin Angiotensin Aldosterone Syst., 2001, 2(1), 4-10.
[] [PMID: 11881054]
Fillion, D.; Cabana, J.; Guillemette, G.; Leduc, R.; Lavigne, P.; Escher, E. Structure of the human angiotensin II type 1 (AT1) receptor bound to angiotensin II from multiple chemoselective photoprobe contacts reveals a unique peptide binding mode. J. Biol. Chem., 2013, 288(12), 8187-8197.
[] [PMID: 23386604]
Shanmugam, S.; Corvol, P.; Gasc, J.M. Ontogeny of the two angiotensin II type 1 receptor subtypes in rats. Am. J. Physiol., 1994, 267(6 Pt 1), E828-E836.
[PMID: 7810623]
Iwai, N.; Inagami, T. Identification of two subtypes in the rat type I angiotensin II receptor. FEBS Lett., 1992, 298(2-3), 257-260.
[] [PMID: 1544458]
Sasamura, H.; Hein, L.; Krieger, J.E.; Pratt, R.E.; Kobilka, B.K.; Dzau, V.J. Cloning, characterization, and expression of two angiotensin receptor (AT-1) isoforms from the mouse genome. Biochem. Biophys. Res. Commun., 1992, 185(1), 253-259.
[] [PMID: 1599461]
Kakar, S.S.; Riel, K.K.; Neill, J.D. Differential expression of angiotensin II receptor subtype mRNAs (AT-1A and AT-1B) in the brain. Biochem. Biophys. Res. Commun., 1992, 185(2), 688-692.
[] [PMID: 1610361]
Johren, O.; Inagami, T.; Saavedra, J.M. AT1A, AT1B, and AT2 angiotensin II receptor subtype gene expression in rat brain. Neuroreport, 1995, 6(18), 2549-2552.
[] [PMID: 8741760]
Burson, J.M.; Aguilera, G.; Gross, K.W.; Sigmund, C.D. Differential expression of angiotensin receptor 1A and 1B in mouse. Am. J. Physiol., 1994, 267(2 Pt 1), E260-E267.
[PMID: 8074205]
Li, J.M.; Shah, A.M. Mechanism of endothelial cell NADPH oxidase activation by angiotensin II. Role of the p47phox subunit. J. Biol. Chem., 2003, 278(14), 12094-12100.
[] [PMID: 12560337]
Beresford, M.J.; Fitzsimons, J.T. Intracerebroventricular angiotensin II-induced thirst and sodium appetite in rat are blocked by the AT1 receptor antagonist, Losartan (DuP 753), but not by the AT2 antagonist, CGP 42112B. Exp. Physiol., 1992, 77(5), 761-764.
[] [PMID: 1418958]
Weisinger, R.S.; Blair-West, J.R.; Burns, P.; Denton, D.A.; Tarjan, E. Role of brain angiotensin in thirst and sodium appetite of rats. Peptides, 1997, 18(7), 977-984.
[] [PMID: 9357055]
Daniels, D. Mietlicki, E.G.; Nowak, E.L.; Fluharty, S.J. Angiotensin II stimulates water and salt intake through separate cell signaling pathway in rats. Exp. Physiol., 2009, 94, 130-137.
[] [PMID: 18723579]
Ferguson, A.V. Angiotensinergic regulation of autonomic and neuroendocrine outputs: critical roles for the subfornical organ and paraventricular nucleus. Neuroendocrinology, 2009, 89(4), 370-376.
[] [PMID: 19342823]
Faraco, G.; Iadecola, C. Hypertension: a harbinger of stroke and dementia. Hypertension, 2013, 62(5), 810-817.
[] [PMID: 23980072]
Biancardi, V.C.; Son, S.J.; Ahmadi, S.; Filosa, J.A.; Stern, J.E. Circulating angiotensin II gains access to the hypothalamus and brain stem during hypertension via breakdown of the blood-brain barrier. Hypertension, 2014, 63(3), 572-579.
[] [PMID: 24343120]
Brooks, V.L.; Scrogin, K.E.; McKeogh, D.F. The interaction of angiotensin II and osmolality in the generation of sympathetic tone during changes in dietary salt intake. An hypothesis. Ann. N. Y. Acad. Sci., 2001, 940, 380-394.
[] [PMID: 11458694]
Carey, R.M.; Wang, Z.Q.; Siragy, H.M. Role of the angiotensin type 2 receptor in the regulation of blood pressure and renal function. Hypertension, 2000, 35(1 Pt 2), 155-163.
[] [PMID: 10642292]
Liu, K.L.; Lo, M.; Grouzmann, E.; Mutter, M.; Sassard, J. The subtype 2 of angiotensin II receptors and pressure-natriuresis in adult rat kidneys. Br. J. Pharmacol., 1999, 126(3), 826-832.
[] [PMID: 10188997]
Morimoto, S.; Sigmund, C.D. Angiotensin mutant mice: a focus on the brain renin-angiotensin system. Neuropeptides, 2002, 36(2-3), 194-200.
[] [PMID: 12359509]
Bader, M.; Peters, J.; Baltatu, O.; Müller, D.N.; Luft, F.C.; Ganten, D. Tissue renin-angiotensin systems: new insights from experimental animal models in hypertension research. J. Mol. Med. (Berl.), 2001, 79(2-3), 76-102.
[] [PMID: 11357942]
Engeli, S.; Negrel, R.; Sharma, A.M. Physiology and pathophysiology of the adipose tissue renin-angiotensin system. Hypertension, 2000, 35(6), 1270-1277.
[] [PMID: 10856276]
Sernia, C. A critical appraisal of the intrinsic pancreatic angiotensin-generating system. JOP, 2001, 2(1), 50-55.
[PMID: 11862023]
Nielsen, A.H.; Schauser, K.H.; Poulsen, K. Current topic: the uteroplacental renin-angiotensin system. Placenta, 2000, 21(5-6), 468-477.
[] [PMID: 10940196]
Navar, L.G.; Imig, J.D.; Zou, L.; Wang, C.T. Intrarenal production of angiotensin II. Semin. Nephrol., 1997, 17(5), 412-422.
[PMID: 9316209]
Shan, Z.; Shi, P.; Cuadra, A.E.; Dong, Y.; Lamont, G.J.; Li, Q.; Seth, D.M.; Navar, L.G.; Katovich, M.J.; Sumners, C.; Raizada, M.K. Involvement of the brain (pro)renin receptor in cardiovascular homeostasis. Circ. Res., 2010, 107(7), 934-938.
[] [PMID: 20689062]
Li, W.; Peng, H.; Mehaffey, E.P.; Kimball, C.D.; Grobe, J.L.; van Gool, J.M.; Sullivan, M.N.; Earley, S.; Danser, A.H.; Ichihara, A.; Feng, Y. Neuron-specific (pro)renin receptor knockout prevents the development of salt-sensitive hypertension. Hypertension, 2014, 63(2), 316-323.
[] [PMID: 24246383]
Li, W.; Sullivan, M.N.; Zhang, S.; Worker, C.J.; Xiong, Z.; Speth, R.C.; Feng, Y. Intracerebroventricular infusion of the (Pro)renin receptor antagonist PRO20 attenuates deoxycorticosterone acetate-salt-induced hypertension. Hypertension, 2015, 65(2), 352-361.
[] [PMID: 25421983]
Hilzendeger, A.M.; Cassell, M.D.; Davis, D.R.; Stauss, H.M.; Mark, A.L.; Grobe, J.L.; Sigmund, C.D. Angiotensin type 1a receptors in the subfornical organ are required for deoxycorticosterone acetate-salt hypertension. Hypertension, 2013, 61(3), 716-722.
[] [PMID: 23266541]
Zubcevic, J.; Waki, H.; Raizada, M.K.; Paton, J.F. Autonomic-immune-vascular interaction: an emerging concept for neurogenic hypertension. Hypertension, 2011, 57(6), 1026-1033.
[] [PMID: 21536990]
Marvar, P.J.; Thabet, S.R.; Guzik, T.J.; Lob, H.E.; McCann, L.A.; Weyand, C.; Gordon, F.J.; Harrison, D.G. Central and peripheral mechanisms of T-lymphocyte activation and vascular inflammation produced by angiotensin II-induced hypertension. Circ. Res., 2010, 107(2), 263-270.
[] [PMID: 20558826]
Lob, H.E.; Marvar, P.J.; Guzik, T.J.; Sharma, S.; McCann, L.A.; Weyand, C.; Gordon, F.J.; Harrison, D.G. Induction of hypertension and peripheral inflammation by reduction of extracellular superoxide dismutase in the central nervous system. Hypertension, 2010, 55(2), 277-283, 6p, 283.
[] [PMID: 20008675]
Lob, H.E.; Schultz, D.; Marvar, P.J.; Davisson, R.L.; Harrison, D.G. Role of the NADPH oxidases in the subfornical organ in angiotensin II-induced hypertension. Hypertension, 2013, 61(2), 382-387.
[] [PMID: 23248154]
Abboud, F.M.; Harwani, S.C.; Chapleau, M.W. Autonomic neural regulation of the immune system: implications for hypertension and cardiovascular disease. Hypertension, 2012, 59(4), 755-762.
[] [PMID: 22331383]
Ganta, C.K.; Lu, N.; Helwig, B.G.; Blecha, F.; Ganta, R.R.; Zheng, L.; Ross, C.R.; Musch, T.I.; Fels, R.J.; Kenney, M.J. Central angiotensin II-enhanced splenic cytokine gene expression is mediated by the sympathetic nervous system. Am. J. Physiol. Heart Circ. Physiol., 2005, 289(4), H1683-H1691.
[] [PMID: 15908469]
Jun, J.Y.; Zubcevic, J.; Qi, Y.; Afzal, A.; Carvajal, J.M.; Thinschmidt, J.S.; Grant, M.B.; Mocco, J.; Raizada, M.K. Brain-mediated dysregulation of the bone marrow activity in angiotensin II-induced hypertension. Hypertension, 2012, 60(5), 1316-1323.
[] [PMID: 23045460]
Gehrmann, J.; Matsumoto, Y.; Kreutzberg, G.W. Microglia: intrinsic immuneffector cell of the brain. Brain Res. Brain Res. Rev., 1995, 20(3), 269-287.
[] [PMID: 7550361]
Shi, P.; Diez-Freire, C.; Jun, J.Y.; Qi, Y.; Katovich, M.J.; Li, Q.; Sriramula, S.; Francis, J.; Sumners, C.; Raizada, M.K. Brain microglial cytokines in neurogenic hypertension. Hypertension, 2010, 56(2), 297-303.
[] [PMID: 20547972]
Waki, H.; Gouraud, S.S.; Maeda, M.; Raizada, M.K.; Paton, J.F. Contributions of vascular inflammation in the brainstem for neurogenic hypertension. Respir. Physiol. Neurobiol., 2011, 178(3), 422-428.
[] [PMID: 21601658]
Fitzsimons, J.T. Angiotensin, thirst, and sodium appetite. Physiol. Rev., 1998, 78(3), 583-686.
[] [PMID: 9674690]
Landas, S.; Phillips, M.I.; Stamler, J.F.; Raizada, M.K. Visualization of specific angiotensin II binding sites in the brain by fluorescent microscopy. Science, 1980, 210(4471), 791-793.
[] [PMID: 6254147]
Mendelsohn, F.A.; Quirion, R.; Saavedra, J.M.; Aguilera, G.; Catt, K.J. Autoradiographic localization of angiotensin II receptors in rat brain. Proc. Natl. Acad. Sci. USA, 1984, 81(5), 1575-1579.
[] [PMID: 6324205]
Ganong, W.F. Circumventricular organs: definition and role in the regulation of endocrine and autonomic function. Clin. Exp. Pharmacol. Physiol., 2000, 27(5-6), 422-427.
[] [PMID: 10831247]
Simpson, J.B. The circumventricular organs and the central actions of angiotensin. Neuroendocrinology, 1981, 32(4), 248-256.
[] [PMID: 7012657]
Gebke, E.; Müller, A.R.; Jurzak, M.; Gerstberger, R. Angiotensin II-induced calcium signalling in neurons and astrocytes of rat circumventricular organs. Neuroscience, 1998, 85(2), 509-520.
[] [PMID: 9622248]
Lenkei, Z.; Palkovits, M.; Corvol, P.; Llorens-Cortès, C. Expression of angiotensin type-1 (AT1) and type-2 (AT2) receptor mRNAs in the adult rat brain: a functional neuroanatomical review. Front. Neuroendocrinol., 1997, 18(4), 383-439.
[] [PMID: 9344632]
McKinley, M.J.; Albiston, A.L.; Allen, A.M.; Mathai, M.L.; May, C.N.; McAllen, R.M.; Oldfield, B.J.; Mendelsohn, F.A.; Chai, S.Y. The brain renin-angiotensin system: location and physiological roles. Int. J. Biochem. Cell Biol., 2003, 35(6), 901-918.
[] [PMID: 12676175]
Mimee, A.; Smith, P.M.; Ferguson, A.V. Circumventricular organs: targets for integration of circulating fluid and energy balance signals? Physiol. Behav., 2013, 121, 96-102.
[] [PMID: 23458630]
Abdelaal, A.E.; Assaf, S.Y.; Kucharczyk, J.; Mogenson, G.J. Effect of ablation of the subfornical organ on water intake elicited by systemically administered angiotensin-II. Can. J. Physiol. Pharmacol., 1974, 52(6), 1217-1220.
[] [PMID: 4375541]
Morris, M.J.; Wilson, W.L.; Starbuck, E.M.; Fitts, D.A. Forebrain circumventricular organs mediate salt appetite induced by intravenous angiotensin II in rats. Brain Res., 2002, 949(1-2), 42-50.
[] [PMID: 12213298]
Mangiapane, M.L.; Simpson, J.B. Pharmacologic independence of subfornical organ receptors mediating drinking. Brain Res., 1979, 178(2-3), 507-517.
[] [PMID: 509216]
Mangiapane, M.L.; Simpson, J.B. Subfornical organ: forebrain site of pressor and dipsogenic action of angiotensin II. Am. J. Physiol., 1980, 239(5), R382-R389.
[PMID: 7435651]
Phillips, M.I. Functions of angiotensin in the central nervous system. Annu. Rev. Physiol., 1987, 49, 413-435.
[] [PMID: 3551809]
Allen, A.M.; Zhuo, J.; Mendelsohn, F.A. Localization and function of angiotensin AT1 receptors. Am. J. Hypertens., 2000, 13(1 Pt 2), 31S-38S.
[] [PMID: 10678286]
Kadekaro, M.; Cohen, S.; Terrell, M.L.; Lekan, H.; Gary, H., Jr; Eisenberg, H.M. Independent activation of subfornical organ and hypothalamo-neurohypophysial system during administration of angiotensin II. Peptides, 1989, 10(2), 423-429.
[] [PMID: 2502773]
McKinley, M.J.; Badoer, E.; Vivas, L.; Oldfield, B.J. Comparison of c-fos expression in the lamina terminalis of conscious rats after intravenous or intracerebroventricular angiotensin. Brain Res. Bull., 1995, 37(2), 131-137.
[] [PMID: 7606488]
Ono, K.; Toyono, T.; Honda, E.; Inenaga, K. Transient outward K+ currents in rat dissociated subfornical organ neurones and angiotensin II effects. J. Physiol., 2005, 568(Pt 3), 979-991.
[] [PMID: 16123110]
Brody, M.J.; Johnson, A.K. Role of the anteroventral third ventricle (AV3V) region in fluid and electrolyte balance, arterial pressure regulation and hypertension.Frontiers in Neuroendocrinology; Ganong, W.F; Martini, L., Ed.; Raven Press: New York, 1980, Vol. 6, pp. 249-292.
Thrasher, T.N.; Keil, L.C. Regulation of drinking and vasopressin secretion: role of organum vasculosum laminae terminalis. Am. J. Physiol., 1987, 253(1 Pt 2), R108-R120.
[PMID: 3605376]
Richard, D.; Bourque, C.W. Synaptic control of rat supraoptic neurones during osmotic stimulation of the organum vasculosum lamina terminalis in vitro. J. Physiol., 1995, 489(Pt 2), 567-577.
[] [PMID: 8847648]
Hendel, M.D.; Collister, J.P. Sodium balance, arterial pressure, and the role of the subfornical organ during chronic changes in dietary salt. Am. J. Physiol. Heart Circ. Physiol., 2005, 289(1), H426-H431.
[] [PMID: 15734879]
Lind, R.W.; Johnson, A.K. Subfornical organ-median preoptic connections and drinking and pressor responses to angiotensin II. J. Neurosci., 1982, 2(8), 1043-1051.
[] [PMID: 7108583]
Zimmerman, M.C.; Lazartigues, E.; Sharma, R.V.; Davisson, R.L. Hypertension caused by angiotensin II infusion involves increased superoxide production in the central nervous system. Circ. Res., 2004, 95(2), 210-216.
[] [PMID: 15192025]
Wang, G.; Sarkar, P.; Peterson, J.R.; Anrather, J.; Pierce, J.P.; Moore, J.M.; Feng, J.; Zhou, P.; Milner, T.A.; Pickel, V.M.; Iadecola, C.; Davisson, R.L. COX-1-derived PGE2 and PGE2 type 1 receptors are vital for angiotensin II-induced formation of reactive oxygen species and Ca(2+) influx in the subfornical organ. Am. J. Physiol. Heart Circ. Physiol., 2013, 305(10), H1451-H1461.
[] [PMID: 24014678]
Peterson, J.R.; Sharma, R.V.; Davisson, R.L. Reactive oxygen species in the neuropathogenesis of hypertension. Curr. Hypertens. Rep., 2006, 8(3), 232-241.
[] [PMID: 17147922]
Young, C.N.; Cao, X.; Guruju, M.R.; Pierce, J.P.; Morgan, D.A.; Wang, G.; Iadecola, C.; Mark, A.L.; Davisson, R.L. ER stress in the brain subfornical organ mediates angiotensin-dependent hypertension. J. Clin. Invest., 2012, 122(11), 3960-3964.
[] [PMID: 23064361]
Murakami, K.; Ganong, W.F. Site at which angiotensin II acts to stimulates ACTH in vivo. Neuroendocrinology, 1987, 46, 281-285.
Ganong, W.F.; Murakami, K. The role of angiotensin II in the regulation of ACTH secretion. Ann. N. Y. Acad. Sci., 1987, 512, 176-186.
[] [PMID: 2831773]
Keil, L.C.; Summy-Long, J.; Severs, W.B. Release of vasopressin by angiotensin II. Endocrinology, 1975, 96(4), 1063-1065.
[] [PMID: 235417]
McKinley, M.J.; Mathai, M.L.; McAllen, R.M.; McClear, R.C.; Miselis, R.R.; Pennington, G.L.; Vivas, L.; Wade, J.D.; Oldfield, B.J. Vasopressin secretion: osmotic and hormonal regulation by the lamina terminalis. J. Neuroendocrinol., 2004, 16(4), 340-347.
[] [PMID: 15089972]
Iovino, M.; Steardo, L. Vasopressin release to central and peripheral angiotensin II in rats with lesions of the subfornical organ. Brain Res., 1984, 322(2), 365-368.
[] [PMID: 6509326]
Knepel, W.; Nutto, D.; Meyer, D.K. Effect of transection of subfornical organ efferent projections on vasopressin release induced by angiotensin or isoprenaline in the rat. Brain Res., 1982, 248(1), 180-184.
[] [PMID: 6289992]
Saavedra, J.M.; Israel, A.; Plunkett, L.M.; Kurihara, M.; Shigematsu, K.; Correa, F.M. Quantitative distribution of angiotensin II binding sites in rat brain by autoradiography. Peptides, 1986, 7(4), 679-687.
[] [PMID: 3763440]
Edwards, G.L.; Ritter, R.C. Area postrema lesions increase drinking to angiotensin and extracellular dehydration. Physiol. Behav., 1982, 29(5), 943-947.
[] [PMID: 7156231]
Ryan, P.J. The neurocircuitry of fluid satiation. Physiol. Rep, 2018, 6(12) e 13744
Iovino, M.; Papa, M.; Monteleone, P.; Steardo, L. Neuroanatomical and biochemical evidence for the involvement of the area postrema in the regulation of vasopressin release in rats. Brain Res., 1988, 447(1), 178-182.
[] [PMID: 3382949]
Arima, H.; Kondo, K.; Murase, T.; Yokoi, H.; Iwasaki, Y.; Saito, H.; Oiso, Y. Regulation of vasopressin synthesis and release by area postrema in rats. Endocrinology, 1998, 139(4), 1481-1486.
[] [PMID: 9528924]
Xu, L.; Collister, J.P.; Osborn, J.W.; Brooks, V.L. Endogenous ANG II supports lumbar sympathetic activity in conscious sodium-deprived rats: role of area postrema. Am. J. Physiol., 1998, 275(1), R46-R55.
[PMID: 9688959]
Fink, G.D.; Bruner, C.A.; Mangiapane, M.L. Area postrema is critical for angiotensin-induced hypertension in rats. Hypertension, 1987, 9(4), 355-361.
[] [PMID: 3557601]
Collister, J.P.; Osborn, J.W. Area postrema lesion attenuates the long-term hypotensive effects of losartan in salt-replete rats. Am. J. Physiol., 1998, 274(2), R357-R366.
[PMID: 9486292]
Nahey, D.B.; Collister, J.P. ANG II-induced hypertension and the role of the area postrema during normal and increased dietary salt. Am. J. Physiol. Heart Circ. Physiol., 2007, 292(1), H694-H700.
[] [PMID: 16980346]
Sirett, N.E.; McLean, A.S.; Bray, J.J.; Hubbard, J.I. Distribution of angiotensin II receptors in rat brain. Brain Res., 1977, 122(2), 299-312.
[] [PMID: 189877]
Huwyler, T.; Felix, D. Angiotensin II-sensitive neurons in septal areas of the rat. Brain Res., 1980, 195(1), 187-195.
[] [PMID: 6249440]
Simonnet, G.; Bioulac, B.; Rodriguez, F.; Vincent, J.D. Evidence of a direct action of angiotensin II on neurones in the septum and in the medial preoptic area. Pharmacol. Biochem. Behav., 1980, 13(3), 359-363.
[] [PMID: 7422691]
Gallagher, J.P.; Zheng, F.; Hasuo, H.; Shinnick-Gallagher, P. Activities of neurons within the rat dorsolateral septal nucleus (DLSN). Prog. Neurobiol., 1995, 45(5), 373-395.
[] [PMID: 7617889]
Black, S.L.; Mogenson, G.J. The regulation of serum sodium in septal lesioned rats: a test of two hypotheses. Physiol. Behav., 1973, 10(2), 379-384.
[] [PMID: 4708503]
Mogenson, G.J. Septal-hypothalamic relationships.De France J.F. The Septal Nuclei; Plenum Press: New York, 1976, pp. 149-184.
Tondat, L.M.; Almli, C.R. Hyperdipsia produced by severing ventral septal fiber systems. Physiol. Behav., 1975, 15(6), 701-706.
[] [PMID: 1226407]
Iovino, M.; Poenaru, S.; Annunziato, L. Basal and thirst-evoked vasopressin secretion in rats with electrolytic lesion of the medio-ventral septal area. Brain Res., 1983, 258(1), 123-126.
[] [PMID: 24010174]
Iovino, M.; Steardo, L. [Effects of septal lesions on the response of vasopressin to angiotensin II] Ann. Endocrinol. (Paris), 1985, 46(2), 113-117.
[PMID: 4037704]
Iovino, M.; Steardo, L. Thirst and vasopressin secretion following central administration of angiotensin II in rats with lesions of the septal area and subfornical organ. Neuroscience, 1985, 15(1), 61-67.
[] [PMID: 4010935]
Iovino, M.; Steardo, L. The role of the septal area in the regulation of drinking behavior and plasma ADH secretion.De Caro G., Epstein A.N. and Massi, M. The Physiology of Thirst and Sodium Appetite; Plenum Press: New York, 1986, pp. 367-374.
Iovino, M.; Monteleone, P.; Papa, M.; Amoruso, A.; Steardo, L. Selective damage of neuron perikarya in the medial septum of the rat forebrain: effects on food and water intake, urine output and body weight. Neurosci. Res., 1988, 6(1), 76-82.
[] [PMID: 3200521]
Saad, W.A.; Guarda, I.F.; Camargo, L.A.; Santos, T.A.; Simões, S.; Saad, W.A. Adrenoceptors of the medial septal area modulate water intake and renal excretory function induced by central administration of angiotensin II. Braz. J. Med. Biol. Res., 2002, 35(8), 951-959.
[] [PMID: 12185387]
Camargo, L.A.; Saad, W.A. Role of the alpha(1)- and alpha(2)-adrenoceptors of the paraventricular nucleus on the water and salt intake, renal excretion, and arterial pressure induced by angiotensin II injection into the medial septal area. Brain Res. Bull., 2001, 54(6), 595-602.
[] [PMID: 11403985]
Colombari, D.S.; Haibara, A.S.; Camargo, L.A.; Saad, W.A.; Renzi, A.; DeLuca, L.A., Jr; Menani, J.V. Role of the medial septal area on the cardiovascular, fluid and electrolytic responses to angiotensin II and cholinergic activation into the subfornical organ in rats. Brain Res. Bull., 1994, 33(3), 249-254.
[] [PMID: 8293310]
Galaverna, O.; De Luca, L.A., Jr; Schulkin, J.; Yao, S.Z.; Epstein, A.N. Deficits in NaCl ingestion after damage to the central nucleus of the amygdala in the rat. Brain Res. Bull., 1992, 28(1), 89-98.
[] [PMID: 1540849]
Seeley, R.J.; Galaverna, O.; Schulkin, J.; Epstein, A.N.; Grill, H.J. Lesions of the central nucleus of the amygdala. II: Effects on intraoral NaCl intake. Behav. Brain Res., 1993, 59(1-2), 19-25.
[] [PMID: 8155286]
Hu, B.; Qiao, H.; Sun, B.; Jia, R.; Fan, Y.; Wang, N.; Lu, B.; Yan, J.Q. AT1 receptor blockade in the central nucleus of the amygdala attenuates the effects of muscimol on sodium and water intake. Neuroscience, 2015, 307, 302-310.
[] [PMID: 26344240]
Yan, J.B.; Sun, H.L.; Wang, Q.; Chen, K.; Sun, B.; Song, L.; Yan, W.; Zhao, X.L.; Zhao, S.R.; Zhang, Y.; Qiao, H.; Hu, B.; Yan, J.Q. Natriorexigenic effect of DAMGO is decreased by blocking AT1 receptors in the central nucleus of the amygdala. Neuroscience, 2014, 262, 9-20.
[] [PMID: 24389419]
von Bohlen und Halbach. O.; Albrecht, D. Van Bohlen und Halbach. Visualization of specific angiotensin II binding sites in the rat limbic system. Neuropeptides, 1998, 32(3), 241-245.
[] [PMID: 10189058]
Chai, S.Y.; Mendelsohn, F.A.; Paxinos, G. Angiotensin converting enzyme in rat brain visualized by quantitative in vitro autoradiography. Neuroscience, 1987, 20(2), 615-627.
[] [PMID: 3035425]
Iovino, M.; Guastamacchia, E.; Giagulli, V.A.; Fiore, G.; Licchelli, B.; Iovino, E.; Triggiani, V. Role of central and peripheral chemoreceptors in vasopressin secretion control. Endocr. Metab. Immune Disord. Drug Targets, 2013, 13(3), 250-255.
[] [PMID: 24032393]
Albecht, D.; Nitschke, T. van Bohlen und Halbach, O. Various effects of angiotensin II on amygdaloid neuronal activity in normotensive control and hypertensive transgenic [TGR (mREN-2) 27] rats. FASEB J., 2000, 13, 925-931.
Schulkin, J.; Marini, J.; Epstein, A.N. A role for the medial region of the amygdala in mineralocorticoid-induced salt hunger. Behav. Neurosci., 1989, 103(1), 179-185.
[] [PMID: 2923671]
Massi, M.; Gentili, L.; Perfumi, M.; de Caro, G.; Schulkin, J. Inhibition of salt appetite in the rat following injection of tachykinins into the medial amygdala. Brain Res., 1990, 513(1), 1-7.
[] [PMID: 1693538]
Zhang, D.M.; Epstein, A.N.; Schulkin, J. Medial region of the amygdala: involvement in adrenal-steroid-induced salt appetite. Brain Res., 1993, 600(1), 20-26.
[] [PMID: 8422586]
Kalia, M.P. Localization of aortic and carotid baroreceptor and chemoreceptor primary afferents in the brain stem.Central nervous system mechnaisms in hypertension; Buckeley, J.P; Ferrario, C.M., Ed.; Raven Press: New York, 1981, pp. 9-24.
Andrews, C.O.; Crim, J.W.; Hartle, D.K. Angiotensin II binding in area postrema and nucleus tractus solitarius of SHR and WKY rats. Brain Res. Bull., 1993, 32(4), 419-424.
[] [PMID: 8221131]
Plunkett, L.M.; Saavedra, J.M. Increased angiotensin II binding affinity in the nucleus tractus solitarius of spontaneously hypertensive rats. Proc. Natl. Acad. Sci. USA, 1985, 82(22), 7721-7724.
[] [PMID: 3865191]
Sved, A.F.; Imaizumi, T.; Talman, W.T.; Reis, D.J. Vasopressin contributes to hypertension caused by nucleus tractus solitarius lesions. Hypertension, 1985, 7(2), 262-267.
[] [PMID: 2858449]
Iovino, M.; Vanacore, A.; Steardo, L. Alpha 2-adrenergic stimulation within the nucleus tractus solitarius attenuates vasopressin release induced by depletion of cardiovascular volume. Pharmacol. Biochem. Behav., 1990, 37(4), 821-824.
[] [PMID: 1982697]
Casto, R.; Phillips, M.I. Mechanism of pressor effects by angiotensin in the nucleus tractus solitarius of rats. Am. J. Physiol., 1984, 247(3 Pt 2), R575-R581.
[PMID: 6089597]
Casto, R.; Phillips, M.I. Angiotensin II attenuates baroreflexes at nucleus tractus solitarius of rats. Am. J. Physiol., 1986, 250(2 Pt 2), R193-R198.
[PMID: 3946636]
Wang, G.; Anrather, J.; Huang, J.; Speth, R.C.; Pickel, V.M.; Iadecola, C. NADPH oxidase contributes to angiotensin II signaling in the nucleus tractus solitarius. J. Neurosci., 2004, 24(24), 5516-5524.
[] [PMID: 15201324]
Wang, G.; Anrather, J.; Glass, M.J.; Tarsitano, M.J.; Zhou, P.; Frys, K.A.; Pickel, V.M.; Iadecola, C. Nox2, Ca2+, and protein kinase C play a role in angiotensin II-induced free radical production in nucleus tractus solitarius. Hypertension, 2006, 48(3), 482-489.
[] [PMID: 16894058]
Iovino, M.; Giagulli, V.A.; Licchelli, B.; Iovino, E.; Guastamacchia, E.; Triggiani, V. Synaptic Inputs of Neural Afferent Pathways to Vasopressin- and Oxytocin-Secreting Neurons of Supraoptic and Paraventricular Hypothalamic Nuclei. Endocr. Metab. Immune Disord. Drug Targets, 2016, 16(4), 276-287.
[] [PMID: 28056741]
Iovino, M.; Guastamacchia, E.; Giagulli, V.A.; Licchelli, B.; Iovino, E.; Triggiani, V. Molecular mechanisms involved in the control of neurohypophyseal hormones secretion. Curr. Pharm. Des., 2014, 20(42), 6702-6713.
[] [PMID: 25190061]
Iovino, M.; Guastamacchia, E.; Giagulli, V.A.; Licchelli, B.; Triggiani, V. Vasopressin secretion control: central neural pathways, neurotransmitters and effects of drugs. Curr. Pharm. Des., 2012, 18(30), 4714-4724.
[] [PMID: 22794200]

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Year: 2020
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DOI: 10.2174/1871530319666190617160934
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