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Article ; Online: Angiotensinergic neurotransmission in the peripheral autonomic nervous system.

Bohlender, Jurgen / Imboden, Hans

Frontiers in bioscience (Landmark edition)

2012 Volume 17, Issue 7, Page(s) 2419–2432

Abstract: Angiotensin (Ang) II has for long been identified as a neuropeptide located within neurons and pathways of the central nervous system involved in the control of thirst and cardio-vascular homeostasis. The presence of Ang II in ganglionic neurons of ... ...

Abstract	Angiotensin (Ang) II has for long been identified as a neuropeptide located within neurons and pathways of the central nervous system involved in the control of thirst and cardio-vascular homeostasis. The presence of Ang II in ganglionic neurons of celiac, dorsal root, and trigeminal ganglia has only recently been described in humans and rats. Ang II-containing fibers were also found in the mesenteric artery and the heart, together with intrinsic Ang II-containing cardiac neurons. Ganglionic neurons express angiotensinogen and co-localize it with Ang II. Its intraneuronal production as a neuropeptide appears to involve angiotensinogen processing enzymes other than renin. Immunocytochemical and gene expression data suggest that neuronal Ang II acts as a neuromodulatory peptide and co-transmitter in the peripheral autonomic, and also sensory nervous system. Neuronal Ang II probably competes with humoral Ang II for effector cell activation. Its functional role, however, still remains to be determined. Angiotensinergic neurotransmission in the autonomic nervous system is a potential new target for therapeutic interventions in many common diseases such as essential hypertension, heart failure, and cardiac arrhythmia.
MeSH term(s)	Angiotensin II/physiology ; Animals ; Autonomic Nervous System/physiology ; Brain/physiology ; Ganglia, Spinal/physiology ; Heart/innervation ; Humans ; Models, Neurological ; Neuropeptides/physiology ; Rats ; Renin/physiology ; Sensory Receptor Cells/physiology ; Sympathetic Nervous System/physiology ; Synaptic Transmission/physiology ; Trigeminal Ganglion/physiology
Chemical Substances	Neuropeptides ; Angiotensin II (11128-99-7) ; Renin (EC 3.4.23.15)
Language	English
Publishing date	2012-06-01
Publishing country	Singapore
Document type	Journal Article ; Review
ZDB-ID	2704569-9
ISSN	2768-6698 ; 1093-9946
ISSN (online)	2768-6698
ISSN	1093-9946
DOI	10.2741/4062
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Article ; Online: Angiotensinergic Innervation of the Human Right Atrium: Implications for Cardiac Reflexes.

Bohlender, Jürgen M / Nussberger, Jürg / Tevaearai, Hendrik / Imboden, Hans

American journal of hypertension

2017 Volume 31, Issue 2, Page(s) 188–196

Abstract: Background: The right atrium is densely innervated and provides sensory input to important cardiocirculatory reflexes controlling cardiac output and blood pressure. Its angiotensin (Ang) II-expressing innervation may release Ang II as a neuropeptide ... ...

Abstract	Background: The right atrium is densely innervated and provides sensory input to important cardiocirculatory reflexes controlling cardiac output and blood pressure. Its angiotensin (Ang) II-expressing innervation may release Ang II as a neuropeptide cotransmitter to modulate reflexes but has not yet been characterized. Methods: Intraoperative surgical biopsies from human right atria (n = 7) were immunocytologically stained for Ang II, tyrosine hydroxylase (TH), and synaptophysin (SYN). Tissue angiotensins were extracted and quantified by radioimmunoassay. Results: Angiotensinergic fibers were frequent in epicardial nerves and around vessels with variable TH co-localization (none to >50%/bundle). Fibers were also widely distributed between cardiomyocytes and in the endocardium where they were typically nonvaricose, TH/SYN-negative and usually accompanied by varicose catecholaminergic fibers. In the endocardium, some showed large varicosities and were partially TH or SYN-positive. A few endocardial regions showed scattered nonvaricose Ang fibers ending directly between endothelial cells. Occasional clusters of thin varicose terminals co-localizing SYN or TH were located underneath, or protruded into, the endothelium. Endocardial density of Ang and TH-positive fibers was 30-300 vs. 200-450/mm2. Atrial Ang II, III, and I concentrations were 67, 16, and 5 fmol/g (median) while Ang IV and V were mostly undetectable. Conclusions: The human right atrium harbors an abundant angiotensinergic innervation and a novel potential source of atrial Ang II. Most peripheral fibers were noncatecholaminergic afferents or preterminal vagal efferents and a minority was presumably sympathetic. Neuronal Ang II release from these fibers may modulate cardiac and circulatory reflexes independently from plasma and tissue Ang II sources.
MeSH term(s)	Aged ; Angiotensin I/analysis ; Angiotensin II/analogs & derivatives ; Angiotensin II/analysis ; Angiotensin III/analysis ; Angiotensins/analysis ; Autonomic Nervous System/chemistry ; Heart Atria/innervation ; Humans ; Male ; Middle Aged ; Nerve Fibers/chemistry ; Peptide Fragments/analysis ; Reflex ; Synaptophysin/analysis ; Tyrosine 3-Monooxygenase/analysis
Chemical Substances	Angiotensins ; Peptide Fragments ; SYP protein, human ; Synaptophysin ; Angiotensin II (11128-99-7) ; Angiotensin III (12687-51-3) ; angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)- (23025-68-5) ; angiotensin pentapeptide (52530-60-6) ; Angiotensin I (9041-90-1) ; Tyrosine 3-Monooxygenase (EC 1.14.16.2)
Language	English
Publishing date	2017-10-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	639383-4
ISSN	1941-7225 ; 1879-1905 ; 0895-7061
ISSN (online)	1941-7225 ; 1879-1905
ISSN	0895-7061
DOI	10.1093/ajh/hpx163
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Zs.A 2329: Show issues

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Article ; Online: Losartan improves cerebrovascular function in a mouse model of Alzheimer's disease with combined overproduction of amyloid-β and transforming growth factor-β1.

Papadopoulos, Panayiota / Tong, Xin-Kang / Imboden, Hans / Hamel, Edith

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

2017 Volume 37, Issue 6, Page(s) 1959–1970

Abstract: Alterations of the renin-angiotensin system have been implicated in the pathogenesis of Alzheimer's disease. We tested the efficacy of losartan (10 mg/kg/day for three months), a selective angiotensin II type 1 receptor antagonist, in alleviating ... ...

Abstract	Alterations of the renin-angiotensin system have been implicated in the pathogenesis of Alzheimer's disease. We tested the efficacy of losartan (10 mg/kg/day for three months), a selective angiotensin II type 1 receptor antagonist, in alleviating cerebrovascular and cognitive deficits in double-transgenic mice (six months at endpoint) that overexpress a mutated form of the human amyloid precursor protein (APP
MeSH term(s)	Alzheimer Disease/drug therapy ; Alzheimer Disease/metabolism ; Alzheimer Disease/physiopathology ; Amyloid beta-Peptides/biosynthesis ; Amyloid beta-Peptides/genetics ; Angiotensin II Type 1 Receptor Blockers/administration & dosage ; Angiotensin II Type 1 Receptor Blockers/therapeutic use ; Animals ; Blood Flow Velocity/drug effects ; Blood Pressure/drug effects ; Cerebrovascular Circulation/drug effects ; Humans ; Losartan/administration & dosage ; Losartan/therapeutic use ; Maze Learning/drug effects ; Memory/drug effects ; Mice, Inbred C57BL ; Mice, Transgenic ; Oxidative Stress/drug effects ; Renin-Angiotensin System/drug effects ; Transforming Growth Factor beta1/biosynthesis ; Transforming Growth Factor beta1/genetics
Chemical Substances	Amyloid beta-Peptides ; Angiotensin II Type 1 Receptor Blockers ; Transforming Growth Factor beta1 ; Losartan (JMS50MPO89)
Language	English
Publishing date	2017-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	604628-9
ISSN	1559-7016 ; 0271-678X
ISSN (online)	1559-7016
ISSN	0271-678X
DOI	10.1177/0271678X16658489
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Zs.A 1663: Show issues

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Article ; Online: Transforming growth factor-β1 induces cerebrovascular dysfunction and astrogliosis through angiotensin II type 1 receptor-mediated signaling pathways.

Ongali, Brice / Nicolakakis, Nektaria / Tong, Xin-Kang / Lecrux, Clotilde / Imboden, Hans / Hamel, Edith

Canadian journal of physiology and pharmacology

2018 Volume 96, Issue 5, Page(s) 527–534

Abstract: Transgenic mice constitutively overexpressing the cytokine transforming growth factor-β1 (TGF-β1) (TGF mice) display cerebrovascular alterations as seen in Alzheimer's disease (AD) and vascular cognitive impairment and dementia (VCID), but no or only ... ...

Abstract	Transgenic mice constitutively overexpressing the cytokine transforming growth factor-β1 (TGF-β1) (TGF mice) display cerebrovascular alterations as seen in Alzheimer's disease (AD) and vascular cognitive impairment and dementia (VCID), but no or only subtle cognitive deficits. TGF-β1 may exert part of its deleterious effects through interactions with angiotensin II (AngII) type 1 receptor (AT1R) signaling pathways. We test such interactions in the brain and cerebral vessels of TGF mice by measuring cerebrovascular reactivity, levels of protein markers of vascular fibrosis, nitric oxide synthase activity, astrogliosis, and mnemonic performance in mice treated (6 months) with the AT1R blocker losartan (10 mg/kg per day) or the angiotensin converting enzyme inhibitor enalapril (3 mg/kg per day). Both treatments restored the severely impaired cerebrovascular reactivity to acetylcholine, calcitonin gene-related peptide, endothelin-1, and the baseline availability of nitric oxide in aged TGF mice. Losartan, but not enalapril, significantly reduced astrogliosis and cerebrovascular levels of profibrotic protein connective tissue growth factor while raising levels of antifibrotic enzyme matrix metallopeptidase-9. Memory was unaffected by aging and treatments. The results suggest a pivotal role for AngII in TGF-β1-induced cerebrovascular dysfunction and neuroinflammation through AT1R-mediated mechanisms. Further, they suggest that AngII blockers could be appropriate against vasculopathies and astrogliosis associated with AD and VCID.
MeSH term(s)	Animals ; Brain/blood supply ; Brain/drug effects ; Enalapril/pharmacology ; Enalapril/therapeutic use ; Female ; Fibrosis ; Gliosis/metabolism ; Gliosis/pathology ; Gliosis/physiopathology ; Losartan/pharmacology ; Losartan/therapeutic use ; Male ; Mice ; Mice, Transgenic ; Receptor, Angiotensin, Type 1/metabolism ; Signal Transduction/drug effects ; Transforming Growth Factor beta1/metabolism
Chemical Substances	Receptor, Angiotensin, Type 1 ; Transforming Growth Factor beta1 ; Enalapril (69PN84IO1A) ; Losartan (JMS50MPO89)
Language	English
Publishing date	2018-03-05
Publishing country	Canada
Document type	Journal Article
ZDB-ID	127527-6
ISSN	1205-7541 ; 0008-4212
ISSN (online)	1205-7541
ISSN	0008-4212
DOI	10.1139/cjpp-2017-0640
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Zs.A 589: Show issues

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Article ; Online: Resetting of renal tissular renin-angiotensin and bradykinin-kallikrein systems after unilateral kidney denervation in rats.

Bohlender, Jürgen M / Nussberger, Jürg / Birkhäuser, Frédéric / Grouzmann, Eric / Thalmann, George N / Imboden, Hans

Histochemistry and cell biology

2017 Volume 147, Issue 5, Page(s) 585–593

Abstract: The renal tissular renin-angiotensin and bradykinin-kallikrein systems control kidney function together with the renal sympathetic innervation but their interaction is still unclear. To further elucidate this relationship, we investigated these systems ... ...

Abstract	The renal tissular renin-angiotensin and bradykinin-kallikrein systems control kidney function together with the renal sympathetic innervation but their interaction is still unclear. To further elucidate this relationship, we investigated these systems in rats 6 days after left kidney denervation (DNX, n = 8) compared to sham-operated controls (CTR, n = 8). Plasma renin concentration was unchanged in DNX vs. CTR (p = NS). Kidney bradykinin (BK) and angiotensin (Ang) I and II concentrations decreased bilaterally in DNX vs. CTR rats (~20 to 40%, p < 0.05) together with Ang IV and V concentrations that were extremely low (p = NS). Renin, Ang III and dopamine concentrations decreased by ~25 to 50% and norepinephrine concentrations by 99% in DNX kidneys (p < 0.05) but were unaltered in opposite kidneys. Ang II/I and KA were comparable in DNX, contralateral and CTR kidneys. Ang III/II increased in right vs. DNX or CTR kidneys (40-50%, p < 0.05). Ang II was mainly located in tubular epithelium by immunocytological staining and its cellular distribution was unaffected by DNX. Moreover, the angiotensinergic and catecholaminergic innervation of right kidneys was unchanged vs. CTR. We found an important dependency of tissular Ang and BK levels on the renal innervation that may contribute to the resetting of kidney function after DNX. The DNX-induced peptide changes were not readily explained by kidney KA, renin or plasma Ang I generation. However, tissular peptide metabolism and compartmentalization may have played a central role. The mechanisms behind the concentration changes remain unclear and deserve further clarification.
Language	English
Publishing date	2017-05
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1222930-1
ISSN	1432-119X ; 0301-5564 ; 0948-6143
ISSN (online)	1432-119X
ISSN	0301-5564 ; 0948-6143
DOI	10.1007/s00418-017-1543-y
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Ub I Zs.94/a: Show issues

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Article ; Online: Angiotensinergic innervation of the kidney: present knowledge and its significance.

Bohlender, Jürgen / Nussberger, Jürg / Imboden, Hans

Current hypertension reports

2012 Volume 15, Issue 1, Page(s) 10–16

Abstract: Intrarenal neurotransmission implies the co-release of neuropeptides at the neuro-effector junction with direct influence on parameters of kidney function. The presence of an angiotensin (Ang) II-containing phenotype in catecholaminergic postganglionic ... ...

Abstract	Intrarenal neurotransmission implies the co-release of neuropeptides at the neuro-effector junction with direct influence on parameters of kidney function. The presence of an angiotensin (Ang) II-containing phenotype in catecholaminergic postganglionic and sensory fibers of the kidney, based on immunocytological investigations, has only recently been reported. These angiotensinergic fibers display a distinct morphology and intrarenal distribution, suggesting anatomical and functional subspecialization linked to neuronal Ang II-expression. This review discusses the present knowledge concerning these fibers, and their significance for renal physiology and the pathogenesis of hypertension in light of established mechanisms. The data suggest a new role of Ang II as a co-transmitter stimulating renal target cells or modulating nerve traffic from or to the kidney. Neuronal Ang II is likely to be an independent source of intrarenal Ang II. Further physiological experimentation will have to explore the role of the angiotensinergic renal innervation and integrate it into existing concepts.
MeSH term(s)	Angiotensin II/physiology ; Animals ; Autonomic Nervous System/physiology ; Endothelium, Vascular/physiology ; Humans ; Hypertension/metabolism ; Immunohistochemistry ; Kidney/innervation ; Kidney/metabolism ; Kidney/physiology ; Neuroeffector Junction/physiology ; Neurons/chemistry ; Neuropeptides/physiology ; Synaptic Transmission/physiology
Chemical Substances	Neuropeptides ; Angiotensin II (11128-99-7)
Language	English
Publishing date	2012-11-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2057367-4
ISSN	1534-3111 ; 1522-6417
ISSN (online)	1534-3111
ISSN	1522-6417
DOI	10.1007/s11906-012-0322-3
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Zs.A 5522: Show issues

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Article ; Online: Enalapril Alone or Co-Administered with Losartan Rescues Cerebrovascular Dysfunction, but not Mnemonic Deficits or Amyloidosis in a Mouse Model of Alzheimer's Disease.

Ongali, Brice / Nicolakakis, Nektaria / Tong, Xing-Kang / Aboulkassim, Tahar / Imboden, Hans / Hamel, Edith

Journal of Alzheimer's disease : JAD

2016 Volume 51, Issue 4, Page(s) 1183–1195

Abstract: The co-administration of angiotensin converting enzyme inhibitors (ACEi) and angiotensin II (AngII) receptor blockers (ARB) that bind angiotensin type 1 receptors (AT1R) may protect from Alzheimer's disease (AD) better than each treatment taken alone. We ...

Abstract	The co-administration of angiotensin converting enzyme inhibitors (ACEi) and angiotensin II (AngII) receptor blockers (ARB) that bind angiotensin type 1 receptors (AT1R) may protect from Alzheimer's disease (AD) better than each treatment taken alone. We tested the curative potential of the non brain-penetrant ACEi enalapril (3 mg/kg/day) administered for 3 months either alone or in combination with the brain penetrant ARB losartan (10 mg/kg/day) in aged (∼15 months) transgenic mice overexpressing a mutated form of the human amyloid-β protein precursor (AβPP, thereafter APP mice). We studied cerebrovascular function, protein levels of oxidative stress markers (superoxide dismutases SOD1, SOD2 and the NADPH oxidase subunit p67phox), amyloid-β (Aβ) pathology, astrogliosis, cholinergic innervation, AT1R and angiotensin IV receptor (AT4R) levels, together with cognitive performance. Both treatments normalized cerebrovascular reactivity and p67phox protein levels, but they did not reduce the cerebrovascular levels of SOD1. Combined treatment normalized cerebrovascular SOD2 levels, significantly attenuated astrogliosis, but did not reduce the increased levels of cerebrovascular AT1R. Yet, combined therapy enhanced thioflavin-S labeled Aβ plaque burden, a tendency not significant when Aβ1 - 42 plaque load was considered. None of the treatments rescued cognitive deficits, cortical AT4R or cholinergic innervation. We conclude that both treatments normalized cerebrovascular function by inhibiting the AngII-induced oxidative stress cascade, and that the positive effects of the combined therapy on astrogliosis were likely due to the ability of losartan to enter brain parenchyma. However, enalapril did not potentiate, and may even dampen, the reported cognitive benefits of losartan, raising caution when selecting the most appropriate antihypertensive therapy in AD patients.
MeSH term(s)	Alzheimer Disease/complications ; Alzheimer Disease/genetics ; Amyloid beta-Peptides/metabolism ; Amyloid beta-Protein Precursor/genetics ; Amyloid beta-Protein Precursor/metabolism ; Amyloidosis/drug therapy ; Amyloidosis/etiology ; Analysis of Variance ; Animals ; Antihypertensive Agents/therapeutic use ; Cerebrovascular Disorders/drug therapy ; Cerebrovascular Disorders/etiology ; Cholinesterases/metabolism ; Disease Models, Animal ; Drug Combinations ; Enalapril/therapeutic use ; Female ; Glial Fibrillary Acidic Protein/metabolism ; Humans ; Losartan/therapeutic use ; Male ; Maze Learning/drug effects ; Memory Disorders/drug therapy ; Memory Disorders/etiology ; Mice ; Mice, Transgenic ; Mutation/genetics
Chemical Substances	Amyloid beta-Peptides ; Amyloid beta-Protein Precursor ; Antihypertensive Agents ; Drug Combinations ; Glial Fibrillary Acidic Protein ; Enalapril (69PN84IO1A) ; Cholinesterases (EC 3.1.1.8) ; Losartan (JMS50MPO89)
Language	English
Publishing date	2016
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-150868
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Zs.A 6084: Show issues

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Article ; Online: Human heart valve-derived scaffold improves cardiac repair in a murine model of myocardial infarction.

Wan, Long / Chen, Yao / Wang, Zhenhua / Wang, Weijun / Schmull, Sebastian / Dong, Jun / Xue, Song / Imboden, Hans / Li, Jun

Scientific reports

2017 Volume 7, Page(s) 39988

Abstract: Cardiac tissue engineering using biomaterials with or without combination of stem cell therapy offers a new option for repairing infarcted heart. However, the bioactivity of biomaterials remains to be optimized because currently available biomaterials do ...

Abstract	Cardiac tissue engineering using biomaterials with or without combination of stem cell therapy offers a new option for repairing infarcted heart. However, the bioactivity of biomaterials remains to be optimized because currently available biomaterials do not mimic the biochemical components as well as the structural properties of native myocardial extracellular matrix. Here we hypothesized that human heart valve-derived scaffold (hHVS), as a clinically relevant novel biomaterial, may provide the proper microenvironment of native myocardial extracellular matrix for cardiac repair. In this study, human heart valve tissue was sliced into 100 μm tissue sheet by frozen-sectioning and then decellularized to form the hHVS. Upon anchoring onto the hHVS, post-infarct murine BM c-kit+ cells exhibited an increased capacity for proliferation and cardiomyogenic differentiation in vitro. When used to patch infarcted heart in a murine model of myocardial infarction, either implantation of the hHVS alone or c-kit+ cell-seeded hHVS significantly improved cardiac function and reduced infarct size; while c-kit+ cell-seeded hHVS was even superior to the hHVS alone. Thus, we have successfully developed a hHVS for cardiac repair. Our in vitro and in vivo observations provide the first clinically relevant evidence for translating the hHVS-based biomaterials into clinical strategies to treat myocardial infarction.
MeSH term(s)	Animals ; Biocompatible Materials ; Bone Marrow Cells/physiology ; Bone Marrow Cells/ultrastructure ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Disease Models, Animal ; Humans ; Male ; Mice, Inbred C57BL ; Mitral Valve/physiology ; Mitral Valve/ultrastructure ; Myocardial Infarction/therapy ; Tissue Engineering/methods ; Tissue Scaffolds
Chemical Substances	Biocompatible Materials
Language	English
Publishing date	2017-01-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep39988
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Article ; Online: Whole body sodium depletion modifies AT1 mRNA expression and serotonin content in the dorsal raphe nucleus.

Porcari, Cintia Yamila / Araujo, Iracema Gomes / Urzedo-Rodrigues, Lilia / De Luca, Laurival Antonio / Menani, José Vanderlei / Caeiro, Ximena Elizabeth / Imboden, Hans / Antunes-Rodrigues, José / Reis, Luís Carlos / Vivas, Laura / Godino, Andrea / Mecawi, André Souza

Journal of neuroendocrinology

2019 Volume 31, Issue 4, Page(s) e12703

Abstract: Angiotensin II (Ang II) acts on Ang II type 1 (AT1) receptors located in the organum vasculosum and subfornical organ (SFO) of the lamina terminalis as a main facilitatory mechanism of sodium appetite. The brain serotonin (5-HT) system with soma located ... ...

Abstract	Angiotensin II (Ang II) acts on Ang II type 1 (AT1) receptors located in the organum vasculosum and subfornical organ (SFO) of the lamina terminalis as a main facilitatory mechanism of sodium appetite. The brain serotonin (5-HT) system with soma located in the dorsal raphe nucleus (DRN) provides a main inhibitory mechanism. In the present study, we first investigated the existence of Ang II AT1 receptors in serotonergic DRN neurones. Then, we examined whether whole body sodium depletion affects the gene expression of the AT1a receptor subtype and the presumed functional significance of AT1 receptors. Using confocal microscopy, we found that tryptophan hydroxylase-2 and serotonin neurones express AT1 receptors in the DRN. Immunofluorescence quantification showed a significant reduction in 5-HT content but no change in AT1 receptor expression or AT1/5-HT colocalisation in the DRN after sodium depletion. Whole body sodium depletion also significantly increased Agtr1a mRNA expression in the SFO and DRN. Oral treatment with the AT1 receptor antagonist losartan reversed the changes in Agtr1a expression in the SFO but not the DRN. Losartan injection into either the DRN or the mesencephalic aqueduct had no influence on sodium depletion-induced 0.3 mol L
MeSH term(s)	Angiotensin II Type 1 Receptor Blockers/pharmacology ; Animals ; Appetite/physiology ; Dorsal Raphe Nucleus/chemistry ; Dorsal Raphe Nucleus/metabolism ; Fluorescent Antibody Technique ; Gene Expression/physiology ; Losartan/pharmacology ; Male ; Neurons/chemistry ; RNA, Messenger/analysis ; Rats ; Rats, Wistar ; Receptor, Angiotensin, Type 1/analysis ; Receptor, Angiotensin, Type 1/genetics ; Receptor, Angiotensin, Type 1/physiology ; Serotonin/analysis ; Sodium/blood ; Sodium/deficiency ; Subfornical Organ/chemistry ; Subfornical Organ/metabolism ; Tryptophan Hydroxylase/analysis
Chemical Substances	Agtr1a protein, rat ; Angiotensin II Type 1 Receptor Blockers ; RNA, Messenger ; Receptor, Angiotensin, Type 1 ; Serotonin (333DO1RDJY) ; Sodium (9NEZ333N27) ; Tryptophan Hydroxylase (EC 1.14.16.4) ; tph2 protein, rat (EC 1.14.16.4) ; Losartan (JMS50MPO89)
Language	English
Publishing date	2019-01-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	1007517-3
ISSN	1365-2826 ; 0953-8194
ISSN (online)	1365-2826
ISSN	0953-8194
DOI	10.1111/jne.12703
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Zs.A 2634: Show issues

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Article ; Online: Angiotensinergic innervation of the kidney: Localization and relationship with catecholaminergic postganglionic and sensory nerve fibers.

Bohlender, Jürgen / Pfarrer, Beat / Patil, Jaspal / Nussberger, Jürg / Thalmann, Georg N / Imboden, Hans

Histology and histopathology

2012 Volume 27, Issue 11, Page(s) 1413–1428

Abstract: We describe an angiotensin (Ang) II-containing innervation of the kidney. Cryosections of rat, pig and human kidneys were investigated for the presence of Ang II-containing nerve fibers using a mouse monoclonal antibody against Ang II (4B3). Co-staining ... ...

Abstract	We describe an angiotensin (Ang) II-containing innervation of the kidney. Cryosections of rat, pig and human kidneys were investigated for the presence of Ang II-containing nerve fibers using a mouse monoclonal antibody against Ang II (4B3). Co-staining was performed with antibodies against synaptophysin, tyrosine 3-hydroxylase, and dopamine beta-hydroxylase to detect catecholaminergic efferent fibers and against calcitonin gene-related peptide to detect sensory fibers. Tagged secondary antibodies and confocal light or laser scanning microscopy were used for immunofluorescence detection. Ang II-containing nerve fibers were densely present in the renal pelvis, the subepithelial layer of the urothelium, the arterial nervous plexus, and the peritubular interstitium of the cortex and outer medulla. They were infrequent in central veins and the renal capsule and absent within glomeruli and the renal papilla. Ang II-positive fibers represented phenotypic subgroups of catecholaminergic postganglionic or sensory fibers with different morphology and intrarenal distribution compared to their Ang II-negative counterparts. The Ang II-positive postganglionic fibers were thicker, produced typically fusiform varicosities and preferentially innervated the outer medulla and periglomerular arterioles. Ang II-negative sensory fibers were highly varicose, prevailing in the pelvis and scarce in the renal periphery compared to the rarely varicose Ang II-positive fibers. Neurons within renal microganglia displayed angiotensinergic, catecholaminergic, or combined phenotypes. Our results suggest that autonomic fibers may be an independent source of intrarenal Ang II acting as a neuropeptide co-transmitter or neuromodulator. The angiotensinergic renal innervation may play a distinct role in the neuronal control of renal sodium reabsorption, vasomotion and renin secretion.
MeSH term(s)	Angiotensin II/metabolism ; Animals ; Autonomic Nervous System/metabolism ; Humans ; Kidney/innervation ; Kidney/metabolism ; Male ; Nerve Fibers/metabolism ; Neurons/metabolism ; Rats ; Rats, Inbred WKY ; Swine ; Urothelium/metabolism
Chemical Substances	Angiotensin II (11128-99-7)
Language	English
Publishing date	2012
Publishing country	Spain
Document type	Journal Article
ZDB-ID	83911-5
ISSN	1699-5848 ; 0213-3911
ISSN (online)	1699-5848
ISSN	0213-3911
DOI	10.14670/HH-27.1413
Database	MEDical Literature Analysis and Retrieval System OnLINE

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