Nephroprotective effects of nebivolol in 2K1C rats through regulation of the kidney ROS-ADMA-NO pathway
To evaluate the protective effect of nebivolol against kidney damage and elucidate the underlying mechanism in a two-kidney, one-clip (2K1C) rat model. 2K1C rats were obtained by clipping left renal artery of male Wistar rats and were considered hypertensive when systolic blood pressure (SBP) was ≥1...
Gespeichert in:
Veröffentlicht in: | Pharmacological reports 2018-10, Vol.70 (5), p.917-929 |
---|---|
Hauptverfasser: | , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 929 |
---|---|
container_issue | 5 |
container_start_page | 917 |
container_title | Pharmacological reports |
container_volume | 70 |
creator | Wang, Yan Niu, Mengzhen Yin, Sha Zhang, Fei Shi, Ruizan |
description | To evaluate the protective effect of nebivolol against kidney damage and elucidate the underlying mechanism in a two-kidney, one-clip (2K1C) rat model.
2K1C rats were obtained by clipping left renal artery of male Wistar rats and were considered hypertensive when systolic blood pressure (SBP) was ≥160mmHg 4 weeks after surgery. The 2K1C hypertensive rats were divided into untreated, nebivolol (10mg/kg, ig), and atenolol (80mg/kg, ig) treatment groups. The treatments lasted for 8 weeks. SBP, kidney structure and function, plasma and kidney angiotensin (Ang) II, nitric oxide (NO), asymmetric dimethylarginine (ADMA), and the oxidant status were examined. Kidney protein expression of NADPH oxidase (Nox) isoforms and its subunit p22phox, nitric oxide synthase (NOS) isoforms, protein arginine N-methyltransferase (PRMT) 1, and dimethylarginine dimethylaminohydrolase (DDAH) 1 and 2 was tested by western blotting.
Nebivolol and atenolol exerted similar hypotensive effects. However, atenolol had little effect while nebivolol significantly ameliorated the functional decline and structural damage in the kidney, especially in non-clipped kidney (NCK), which was associated with the reduction of Ang II in NCK. Moreover, nebivolol inhibited the NCK production of reactive oxygen species (ROS) by decreasing Nox2, Nox4, and p22phox expression. Further, nebivolol reduced the plasma and kidney ADMA levels by increasing DDAH2 expression and decreasing PRMT1 expression. Nebivolol also increased the NCK NO level by ameliorating the expression of kidney NOS isoforms.
Our results demonstrated that long-term treatment with nebivolol had renoprotective effect in 2K1C rats partly via regulation of kidney ROS-ADMA-NO pathway. |
doi_str_mv | 10.1016/j.pharep.2018.04.004 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2087993427</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1734114017307363</els_id><sourcerecordid>2087993427</sourcerecordid><originalsourceid>FETCH-LOGICAL-c408t-185da4eeeb29d6e1fcb2f69aeaa196b3b82be00fada251f77e4c57c4fb0649503</originalsourceid><addsrcrecordid>eNqFkUtv3CAURlHUKpk8_kEUsezGLmD8YFNpNH2kSpqRmnaNML6MmXqMC_ZU8-_DyEmWzQqke74P3QNC15SklNDi4zYdWuVhSBmhVUp4Sgg_QQvGhEjyouLv0IKWGU8o5eQMnYewjQBlWX6KzjJChGCiWqDNAwytd4N3I-jR7gGDMfEWsDO4h9ruXec6bHvM7ugKexUnYwxMmxZ72EydGq3rj_DYAv5jmx4O-Of6MVl-_rFMHtZ4UGP7Tx0u0XujugBXz-cF-v31y6_VbXK__vZ9tbxPNCfVmNAqbxQHgJqJpgBqdM1MIRQoRUVRZ3XFaiDEqEaxnJqyBK7zUnNTk4KLnGQX6MPcGzf6O0EY5c4GDV2nenBTkIxUpRAZZ2VE-Yxq70LwYOTg7U75g6REHhXLrZwVy6NiSbiMBmPs5vmFqd5B8xp6cRqBfAZCHPUb8HLrJt_Hrd8q_jTnIPrZ25gL2kKvobE-_ohsnP1_wROZbqFP</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2087993427</pqid></control><display><type>article</type><title>Nephroprotective effects of nebivolol in 2K1C rats through regulation of the kidney ROS-ADMA-NO pathway</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Wang, Yan ; Niu, Mengzhen ; Yin, Sha ; Zhang, Fei ; Shi, Ruizan</creator><creatorcontrib>Wang, Yan ; Niu, Mengzhen ; Yin, Sha ; Zhang, Fei ; Shi, Ruizan</creatorcontrib><description>To evaluate the protective effect of nebivolol against kidney damage and elucidate the underlying mechanism in a two-kidney, one-clip (2K1C) rat model.
2K1C rats were obtained by clipping left renal artery of male Wistar rats and were considered hypertensive when systolic blood pressure (SBP) was ≥160mmHg 4 weeks after surgery. The 2K1C hypertensive rats were divided into untreated, nebivolol (10mg/kg, ig), and atenolol (80mg/kg, ig) treatment groups. The treatments lasted for 8 weeks. SBP, kidney structure and function, plasma and kidney angiotensin (Ang) II, nitric oxide (NO), asymmetric dimethylarginine (ADMA), and the oxidant status were examined. Kidney protein expression of NADPH oxidase (Nox) isoforms and its subunit p22phox, nitric oxide synthase (NOS) isoforms, protein arginine N-methyltransferase (PRMT) 1, and dimethylarginine dimethylaminohydrolase (DDAH) 1 and 2 was tested by western blotting.
Nebivolol and atenolol exerted similar hypotensive effects. However, atenolol had little effect while nebivolol significantly ameliorated the functional decline and structural damage in the kidney, especially in non-clipped kidney (NCK), which was associated with the reduction of Ang II in NCK. Moreover, nebivolol inhibited the NCK production of reactive oxygen species (ROS) by decreasing Nox2, Nox4, and p22phox expression. Further, nebivolol reduced the plasma and kidney ADMA levels by increasing DDAH2 expression and decreasing PRMT1 expression. Nebivolol also increased the NCK NO level by ameliorating the expression of kidney NOS isoforms.
Our results demonstrated that long-term treatment with nebivolol had renoprotective effect in 2K1C rats partly via regulation of kidney ROS-ADMA-NO pathway.</description><identifier>ISSN: 1734-1140</identifier><identifier>EISSN: 2299-5684</identifier><identifier>DOI: 10.1016/j.pharep.2018.04.004</identifier><identifier>PMID: 30099298</identifier><language>eng</language><publisher>Cham: Elsevier B.V</publisher><subject>2K1C hypertension ; Amidohydrolases - biosynthesis ; Angiotensin II - blood ; Angiotensin II - metabolism ; Animals ; Arginine - analogs & derivatives ; Arginine - blood ; Arginine - metabolism ; Atenolol - pharmacology ; Blood Pressure - physiology ; Drug Safety and Pharmacovigilance ; Hypertension, Renovascular - drug therapy ; Hypertension, Renovascular - metabolism ; Kidney ; Kidney - drug effects ; Kidney - injuries ; Kidney - metabolism ; Kidney - pathology ; Kidney Function Tests ; Male ; NADPH Oxidases - biosynthesis ; Nebivolol ; Nebivolol - pharmacology ; Nebivolol - therapeutic use ; Nitric Oxide - blood ; Nitric Oxide - metabolism ; Nitric Oxide Synthase - biosynthesis ; Original Article ; Pharmacotherapy ; Pharmacy ; Protective Agents - pharmacology ; Protective Agents - therapeutic use ; Protein-Arginine N-Methyltransferases - biosynthesis ; Rats ; Reactive Oxygen Species - metabolism ; ROS-ADMA-NO pathway ; Signal Transduction - drug effects</subject><ispartof>Pharmacological reports, 2018-10, Vol.70 (5), p.917-929</ispartof><rights>2018 Institute of Pharmacology, Polish Academy of Sciences</rights><rights>Maj Institute of Pharmacology Polish Academy of Sciences 2018</rights><rights>Copyright © 2018 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c408t-185da4eeeb29d6e1fcb2f69aeaa196b3b82be00fada251f77e4c57c4fb0649503</citedby><cites>FETCH-LOGICAL-c408t-185da4eeeb29d6e1fcb2f69aeaa196b3b82be00fada251f77e4c57c4fb0649503</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1016/j.pharep.2018.04.004$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1016/j.pharep.2018.04.004$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30099298$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Yan</creatorcontrib><creatorcontrib>Niu, Mengzhen</creatorcontrib><creatorcontrib>Yin, Sha</creatorcontrib><creatorcontrib>Zhang, Fei</creatorcontrib><creatorcontrib>Shi, Ruizan</creatorcontrib><title>Nephroprotective effects of nebivolol in 2K1C rats through regulation of the kidney ROS-ADMA-NO pathway</title><title>Pharmacological reports</title><addtitle>Pharmacol. Rep</addtitle><addtitle>Pharmacol Rep</addtitle><description>To evaluate the protective effect of nebivolol against kidney damage and elucidate the underlying mechanism in a two-kidney, one-clip (2K1C) rat model.
2K1C rats were obtained by clipping left renal artery of male Wistar rats and were considered hypertensive when systolic blood pressure (SBP) was ≥160mmHg 4 weeks after surgery. The 2K1C hypertensive rats were divided into untreated, nebivolol (10mg/kg, ig), and atenolol (80mg/kg, ig) treatment groups. The treatments lasted for 8 weeks. SBP, kidney structure and function, plasma and kidney angiotensin (Ang) II, nitric oxide (NO), asymmetric dimethylarginine (ADMA), and the oxidant status were examined. Kidney protein expression of NADPH oxidase (Nox) isoforms and its subunit p22phox, nitric oxide synthase (NOS) isoforms, protein arginine N-methyltransferase (PRMT) 1, and dimethylarginine dimethylaminohydrolase (DDAH) 1 and 2 was tested by western blotting.
Nebivolol and atenolol exerted similar hypotensive effects. However, atenolol had little effect while nebivolol significantly ameliorated the functional decline and structural damage in the kidney, especially in non-clipped kidney (NCK), which was associated with the reduction of Ang II in NCK. Moreover, nebivolol inhibited the NCK production of reactive oxygen species (ROS) by decreasing Nox2, Nox4, and p22phox expression. Further, nebivolol reduced the plasma and kidney ADMA levels by increasing DDAH2 expression and decreasing PRMT1 expression. Nebivolol also increased the NCK NO level by ameliorating the expression of kidney NOS isoforms.
Our results demonstrated that long-term treatment with nebivolol had renoprotective effect in 2K1C rats partly via regulation of kidney ROS-ADMA-NO pathway.</description><subject>2K1C hypertension</subject><subject>Amidohydrolases - biosynthesis</subject><subject>Angiotensin II - blood</subject><subject>Angiotensin II - metabolism</subject><subject>Animals</subject><subject>Arginine - analogs & derivatives</subject><subject>Arginine - blood</subject><subject>Arginine - metabolism</subject><subject>Atenolol - pharmacology</subject><subject>Blood Pressure - physiology</subject><subject>Drug Safety and Pharmacovigilance</subject><subject>Hypertension, Renovascular - drug therapy</subject><subject>Hypertension, Renovascular - metabolism</subject><subject>Kidney</subject><subject>Kidney - drug effects</subject><subject>Kidney - injuries</subject><subject>Kidney - metabolism</subject><subject>Kidney - pathology</subject><subject>Kidney Function Tests</subject><subject>Male</subject><subject>NADPH Oxidases - biosynthesis</subject><subject>Nebivolol</subject><subject>Nebivolol - pharmacology</subject><subject>Nebivolol - therapeutic use</subject><subject>Nitric Oxide - blood</subject><subject>Nitric Oxide - metabolism</subject><subject>Nitric Oxide Synthase - biosynthesis</subject><subject>Original Article</subject><subject>Pharmacotherapy</subject><subject>Pharmacy</subject><subject>Protective Agents - pharmacology</subject><subject>Protective Agents - therapeutic use</subject><subject>Protein-Arginine N-Methyltransferases - biosynthesis</subject><subject>Rats</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>ROS-ADMA-NO pathway</subject><subject>Signal Transduction - drug effects</subject><issn>1734-1140</issn><issn>2299-5684</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtv3CAURlHUKpk8_kEUsezGLmD8YFNpNH2kSpqRmnaNML6MmXqMC_ZU8-_DyEmWzQqke74P3QNC15SklNDi4zYdWuVhSBmhVUp4Sgg_QQvGhEjyouLv0IKWGU8o5eQMnYewjQBlWX6KzjJChGCiWqDNAwytd4N3I-jR7gGDMfEWsDO4h9ruXec6bHvM7ugKexUnYwxMmxZ72EydGq3rj_DYAv5jmx4O-Of6MVl-_rFMHtZ4UGP7Tx0u0XujugBXz-cF-v31y6_VbXK__vZ9tbxPNCfVmNAqbxQHgJqJpgBqdM1MIRQoRUVRZ3XFaiDEqEaxnJqyBK7zUnNTk4KLnGQX6MPcGzf6O0EY5c4GDV2nenBTkIxUpRAZZ2VE-Yxq70LwYOTg7U75g6REHhXLrZwVy6NiSbiMBmPs5vmFqd5B8xp6cRqBfAZCHPUb8HLrJt_Hrd8q_jTnIPrZ25gL2kKvobE-_ohsnP1_wROZbqFP</recordid><startdate>20181001</startdate><enddate>20181001</enddate><creator>Wang, Yan</creator><creator>Niu, Mengzhen</creator><creator>Yin, Sha</creator><creator>Zhang, Fei</creator><creator>Shi, Ruizan</creator><general>Elsevier B.V</general><general>Springer International Publishing</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20181001</creationdate><title>Nephroprotective effects of nebivolol in 2K1C rats through regulation of the kidney ROS-ADMA-NO pathway</title><author>Wang, Yan ; Niu, Mengzhen ; Yin, Sha ; Zhang, Fei ; Shi, Ruizan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c408t-185da4eeeb29d6e1fcb2f69aeaa196b3b82be00fada251f77e4c57c4fb0649503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>2K1C hypertension</topic><topic>Amidohydrolases - biosynthesis</topic><topic>Angiotensin II - blood</topic><topic>Angiotensin II - metabolism</topic><topic>Animals</topic><topic>Arginine - analogs & derivatives</topic><topic>Arginine - blood</topic><topic>Arginine - metabolism</topic><topic>Atenolol - pharmacology</topic><topic>Blood Pressure - physiology</topic><topic>Drug Safety and Pharmacovigilance</topic><topic>Hypertension, Renovascular - drug therapy</topic><topic>Hypertension, Renovascular - metabolism</topic><topic>Kidney</topic><topic>Kidney - drug effects</topic><topic>Kidney - injuries</topic><topic>Kidney - metabolism</topic><topic>Kidney - pathology</topic><topic>Kidney Function Tests</topic><topic>Male</topic><topic>NADPH Oxidases - biosynthesis</topic><topic>Nebivolol</topic><topic>Nebivolol - pharmacology</topic><topic>Nebivolol - therapeutic use</topic><topic>Nitric Oxide - blood</topic><topic>Nitric Oxide - metabolism</topic><topic>Nitric Oxide Synthase - biosynthesis</topic><topic>Original Article</topic><topic>Pharmacotherapy</topic><topic>Pharmacy</topic><topic>Protective Agents - pharmacology</topic><topic>Protective Agents - therapeutic use</topic><topic>Protein-Arginine N-Methyltransferases - biosynthesis</topic><topic>Rats</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>ROS-ADMA-NO pathway</topic><topic>Signal Transduction - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Yan</creatorcontrib><creatorcontrib>Niu, Mengzhen</creatorcontrib><creatorcontrib>Yin, Sha</creatorcontrib><creatorcontrib>Zhang, Fei</creatorcontrib><creatorcontrib>Shi, Ruizan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Pharmacological reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Yan</au><au>Niu, Mengzhen</au><au>Yin, Sha</au><au>Zhang, Fei</au><au>Shi, Ruizan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nephroprotective effects of nebivolol in 2K1C rats through regulation of the kidney ROS-ADMA-NO pathway</atitle><jtitle>Pharmacological reports</jtitle><stitle>Pharmacol. Rep</stitle><addtitle>Pharmacol Rep</addtitle><date>2018-10-01</date><risdate>2018</risdate><volume>70</volume><issue>5</issue><spage>917</spage><epage>929</epage><pages>917-929</pages><issn>1734-1140</issn><eissn>2299-5684</eissn><abstract>To evaluate the protective effect of nebivolol against kidney damage and elucidate the underlying mechanism in a two-kidney, one-clip (2K1C) rat model.
2K1C rats were obtained by clipping left renal artery of male Wistar rats and were considered hypertensive when systolic blood pressure (SBP) was ≥160mmHg 4 weeks after surgery. The 2K1C hypertensive rats were divided into untreated, nebivolol (10mg/kg, ig), and atenolol (80mg/kg, ig) treatment groups. The treatments lasted for 8 weeks. SBP, kidney structure and function, plasma and kidney angiotensin (Ang) II, nitric oxide (NO), asymmetric dimethylarginine (ADMA), and the oxidant status were examined. Kidney protein expression of NADPH oxidase (Nox) isoforms and its subunit p22phox, nitric oxide synthase (NOS) isoforms, protein arginine N-methyltransferase (PRMT) 1, and dimethylarginine dimethylaminohydrolase (DDAH) 1 and 2 was tested by western blotting.
Nebivolol and atenolol exerted similar hypotensive effects. However, atenolol had little effect while nebivolol significantly ameliorated the functional decline and structural damage in the kidney, especially in non-clipped kidney (NCK), which was associated with the reduction of Ang II in NCK. Moreover, nebivolol inhibited the NCK production of reactive oxygen species (ROS) by decreasing Nox2, Nox4, and p22phox expression. Further, nebivolol reduced the plasma and kidney ADMA levels by increasing DDAH2 expression and decreasing PRMT1 expression. Nebivolol also increased the NCK NO level by ameliorating the expression of kidney NOS isoforms.
Our results demonstrated that long-term treatment with nebivolol had renoprotective effect in 2K1C rats partly via regulation of kidney ROS-ADMA-NO pathway.</abstract><cop>Cham</cop><pub>Elsevier B.V</pub><pmid>30099298</pmid><doi>10.1016/j.pharep.2018.04.004</doi><tpages>13</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1734-1140 |
ispartof | Pharmacological reports, 2018-10, Vol.70 (5), p.917-929 |
issn | 1734-1140 2299-5684 |
language | eng |
recordid | cdi_proquest_miscellaneous_2087993427 |
source | MEDLINE; SpringerLink Journals - AutoHoldings |
subjects | 2K1C hypertension Amidohydrolases - biosynthesis Angiotensin II - blood Angiotensin II - metabolism Animals Arginine - analogs & derivatives Arginine - blood Arginine - metabolism Atenolol - pharmacology Blood Pressure - physiology Drug Safety and Pharmacovigilance Hypertension, Renovascular - drug therapy Hypertension, Renovascular - metabolism Kidney Kidney - drug effects Kidney - injuries Kidney - metabolism Kidney - pathology Kidney Function Tests Male NADPH Oxidases - biosynthesis Nebivolol Nebivolol - pharmacology Nebivolol - therapeutic use Nitric Oxide - blood Nitric Oxide - metabolism Nitric Oxide Synthase - biosynthesis Original Article Pharmacotherapy Pharmacy Protective Agents - pharmacology Protective Agents - therapeutic use Protein-Arginine N-Methyltransferases - biosynthesis Rats Reactive Oxygen Species - metabolism ROS-ADMA-NO pathway Signal Transduction - drug effects |
title | Nephroprotective effects of nebivolol in 2K1C rats through regulation of the kidney ROS-ADMA-NO pathway |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-03T13%3A26%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Nephroprotective%20effects%20of%20nebivolol%20in%202K1C%20rats%20through%20regulation%20of%20the%20kidney%20ROS-ADMA-NO%20pathway&rft.jtitle=Pharmacological%20reports&rft.au=Wang,%20Yan&rft.date=2018-10-01&rft.volume=70&rft.issue=5&rft.spage=917&rft.epage=929&rft.pages=917-929&rft.issn=1734-1140&rft.eissn=2299-5684&rft_id=info:doi/10.1016/j.pharep.2018.04.004&rft_dat=%3Cproquest_cross%3E2087993427%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2087993427&rft_id=info:pmid/30099298&rft_els_id=S1734114017307363&rfr_iscdi=true |