- Background/Aims: To investigate the renal phenotype under conditions of an activated renal ET-1 system in the status of nitric oxide deficiency, we compared kidney function and morphology in wild-type, ET-1 transgenic (ET+/+), endothelial nitric oxide synthase knockout (eNOS-/-) and ET+/+eNOS-/- mice. Methods: We assessed blood pressure, parameters of renal morphology, plasma cystatin C, urinary protein excretion, expression of genes associated with glomerular filtration barrier and tissue remodeling, and plasma metabolites using metabolomics. Results: eNOS-/- and ET+/+eNOS-/- mice developed hypertension. Osteopontin, albumin and protein excretion were increased in eNOS-/- and restored in ET+/+eNOS-/- animals. All genetically modified mice developed renal interstitial fibrosis and glomerulosclerosis. Genes involved in tissue remodeling (serpinel, TIMP1, Collal, CCL2) were up-regulated in eNOS-/-, but not in ET+/+eNOS-/- mice. Plasma levels of free carnitine and acylcarnitines, amino acids, diacyl phosphatidylcholines,Background/Aims: To investigate the renal phenotype under conditions of an activated renal ET-1 system in the status of nitric oxide deficiency, we compared kidney function and morphology in wild-type, ET-1 transgenic (ET+/+), endothelial nitric oxide synthase knockout (eNOS-/-) and ET+/+eNOS-/- mice. Methods: We assessed blood pressure, parameters of renal morphology, plasma cystatin C, urinary protein excretion, expression of genes associated with glomerular filtration barrier and tissue remodeling, and plasma metabolites using metabolomics. Results: eNOS-/- and ET+/+eNOS-/- mice developed hypertension. Osteopontin, albumin and protein excretion were increased in eNOS-/- and restored in ET+/+eNOS-/- animals. All genetically modified mice developed renal interstitial fibrosis and glomerulosclerosis. Genes involved in tissue remodeling (serpinel, TIMP1, Collal, CCL2) were up-regulated in eNOS-/-, but not in ET+/+eNOS-/- mice. Plasma levels of free carnitine and acylcarnitines, amino acids, diacyl phosphatidylcholines, lysophosphatidylcholines and hexoses were descreased in eNOS-/- and were in the normal range in ET+/+eNOS-/- mice. Conclusion: eNOS-/- mice developed renal dysfunction, which was partially rescued by ET-1 overexpression in eNOS-/- mice. The metabolomics results suggest that ET-1 overexpression on top of eNOS knockout is associated with a functional recovery of mitochondria (rescue effect in 13-oxidation of fatty acids) and an increase in antioxidative properties (normalization of monounsaturated fatty acids levels). (C) 2015 The Author(s) Published by S. Karger AG, Basel…
MetadatenVerfasserangaben: | Oleg TsuprykovGND, Lyubov Chaykovska, Axel Kretschmer, Johannes-Peter Stasch, Thiemo Pfab, Katharina Krause-Relle, Christoph ReichetzederORCiDGND, Philipp Kalk, Jerzy Adamski, Berthold HocherORCiDGND |
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DOI: | https://doi.org/10.1159/000438516 |
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ISSN: | 1015-8987 |
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ISSN: | 1421-9778 |
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Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/26509263 |
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Titel des übergeordneten Werks (Englisch): | Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology |
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Verlag: | Karger |
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Verlagsort: | Basel |
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Publikationstyp: | Wissenschaftlicher Artikel |
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Sprache: | Englisch |
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Jahr der Erstveröffentlichung: | 2015 |
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Erscheinungsjahr: | 2015 |
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Datum der Freischaltung: | 27.03.2017 |
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Freies Schlagwort / Tag: | Chronic kidney disease; Endothelial nitric oxide synthase; Endothelin; Mice; Nitric oxide |
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Band: | 37 |
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Ausgabe: | 4 |
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Seitenanzahl: | 17 |
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Erste Seite: | 1474 |
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Letzte Seite: | 1490 |
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Fördernde Institution: | German Federal Ministry of Education and Research (BMBF) |
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Organisationseinheiten: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft |
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Peer Review: | Referiert |
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Publikationsweg: | Open Access |
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