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The Relationship between the Intrarenal Dopamine System and Intrarenal Renin-angiotensin System Depending on the Renal Function

Objective The mechanisms underlying the intrarenal renin-angiotensin system (RAS) activation depend on the conditions of kidney diseases. In angiotensin II (AngII) infusion models, the circulating AngII is filtered into the renal tubular lumens, activating intrarenal RAS. However, in the chronic kid...

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Published in:Internal Medicine 2018/11/15, Vol.57(22), pp.3241-3247
Main Authors: Matsuyama, Takashi, Ohashi, Naro, Ishigaki, Sayaka, Isobe, Shinsuke, Tsuji, Naoko, Fujikura, Tomoyuki, Tsuji, Takayuki, Kato, Akihiko, Miyajima, Hiroaki, Yasuda, Hideo
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cited_by cdi_FETCH-LOGICAL-c667t-81f1d8eb7f394d567c02bd85ca6defb28afe422216e04bed1b20e08ebf170f593
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container_issue 22
container_start_page 3241
container_title Internal Medicine
container_volume 57
creator Matsuyama, Takashi
Ohashi, Naro
Ishigaki, Sayaka
Isobe, Shinsuke
Tsuji, Naoko
Fujikura, Tomoyuki
Tsuji, Takayuki
Kato, Akihiko
Miyajima, Hiroaki
Yasuda, Hideo
description Objective The mechanisms underlying the intrarenal renin-angiotensin system (RAS) activation depend on the conditions of kidney diseases. In angiotensin II (AngII) infusion models, the circulating AngII is filtered into the renal tubular lumens, activating intrarenal RAS. However, in the chronic kidney disease (CKD) models, plasma angiotensinogen (AGT) is filtered into the tubular lumens because of glomerular injury, activating intrarenal RAS. The intrarenal dopamine system activation reduces intrarenal AGT expression and suppresses the intrarenal RAS activity in AngII infusion models. However, the relationship between the intrarenal dopamine system and intrarenal RAS has not been elucidated. Therefore, this study was conducted to determine that relationship in CKD patients. Methods We recruited 46 CKD patients (age: 51.1±20.0 years; 16 men; causes of CKD: chronic glomerulonephritis, 34; diabetic nephropathy, 2; nephrosclerosis, 4; and others, 6) not undergoing dialysis or taking RAS blockers. The urinary dopamine (U-DOPA) level, an indicator of intrarenal dopamine activity, and the urinary AGT (U-AGT) level, a surrogate marker of intrarenal RAS activity, were measured. Results As the CKD stages progressed, the U-DOPA levels decreased while the U-AGT levels increased. The U-DOPA levels were significantly and negatively correlated with the U-AGT levels but significantly and positively correlated with the estimated glomerular filtration rate (eGFR). A multiple regression analysis revealed that the U-DOPA levels were associated with the U-AGT levels after adjusting for age, sex, body mass index, and blood pressure (β=-0.38, p=0.045). However, no correlation was observed when eGFR was also adjusted (β=-0.17, p=0.29). Conclusion The negative correlation between the intrarenal dopamine system and intrarenal RAS in CKD patients may be affected by the renal function.
doi_str_mv 10.2169/internalmedicine.0994-18
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In angiotensin II (AngII) infusion models, the circulating AngII is filtered into the renal tubular lumens, activating intrarenal RAS. However, in the chronic kidney disease (CKD) models, plasma angiotensinogen (AGT) is filtered into the tubular lumens because of glomerular injury, activating intrarenal RAS. The intrarenal dopamine system activation reduces intrarenal AGT expression and suppresses the intrarenal RAS activity in AngII infusion models. However, the relationship between the intrarenal dopamine system and intrarenal RAS has not been elucidated. Therefore, this study was conducted to determine that relationship in CKD patients. Methods We recruited 46 CKD patients (age: 51.1±20.0 years; 16 men; causes of CKD: chronic glomerulonephritis, 34; diabetic nephropathy, 2; nephrosclerosis, 4; and others, 6) not undergoing dialysis or taking RAS blockers. The urinary dopamine (U-DOPA) level, an indicator of intrarenal dopamine activity, and the urinary AGT (U-AGT) level, a surrogate marker of intrarenal RAS activity, were measured. Results As the CKD stages progressed, the U-DOPA levels decreased while the U-AGT levels increased. The U-DOPA levels were significantly and negatively correlated with the U-AGT levels but significantly and positively correlated with the estimated glomerular filtration rate (eGFR). A multiple regression analysis revealed that the U-DOPA levels were associated with the U-AGT levels after adjusting for age, sex, body mass index, and blood pressure (β=-0.38, p=0.045). However, no correlation was observed when eGFR was also adjusted (β=-0.17, p=0.29). Conclusion The negative correlation between the intrarenal dopamine system and intrarenal RAS in CKD patients may be affected by the renal function.</description><identifier>ISSN: 0918-2918</identifier><identifier>EISSN: 1349-7235</identifier><identifier>DOI: 10.2169/internalmedicine.0994-18</identifier><identifier>PMID: 29984779</identifier><language>eng</language><publisher>Japan: The Japanese Society of Internal Medicine</publisher><subject>Activation ; Adult ; Angiotensin ; Angiotensin II ; Angiotensinogen ; Blood pressure ; Body mass ; Body mass index ; Diabetes mellitus ; Dialysis ; Dihydroxyphenylalanine ; Dopamine ; Dopamine - metabolism ; Epidermal growth factor receptors ; Female ; Glomerular filtration rate ; Glomerular Filtration Rate - physiology ; Glomerulonephritis ; Humans ; Internal medicine ; intrarenal dopamine system ; kidney ; Kidney - metabolism ; Kidney - physiopathology ; Kidney diseases ; Kidneys ; Lumens ; Male ; Middle Aged ; Multiple regression analysis ; Nephropathy ; Original ; Renal function ; Renal Insufficiency, Chronic - metabolism ; Renal Insufficiency, Chronic - physiopathology ; Renin ; renin-angiotensin system ; Renin-Angiotensin System - physiology ; urinary angiotensinogen</subject><ispartof>Internal Medicine, 2018/11/15, Vol.57(22), pp.3241-3247</ispartof><rights>2018 by The Japanese Society of Internal Medicine</rights><rights>Copyright Japan Science and Technology Agency 2018</rights><rights>Copyright © 2018 by The Japanese Society of Internal Medicine 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c667t-81f1d8eb7f394d567c02bd85ca6defb28afe422216e04bed1b20e08ebf170f593</citedby><cites>FETCH-LOGICAL-c667t-81f1d8eb7f394d567c02bd85ca6defb28afe422216e04bed1b20e08ebf170f593</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287984/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287984/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29984779$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Matsuyama, Takashi</creatorcontrib><creatorcontrib>Ohashi, Naro</creatorcontrib><creatorcontrib>Ishigaki, Sayaka</creatorcontrib><creatorcontrib>Isobe, Shinsuke</creatorcontrib><creatorcontrib>Tsuji, Naoko</creatorcontrib><creatorcontrib>Fujikura, Tomoyuki</creatorcontrib><creatorcontrib>Tsuji, Takayuki</creatorcontrib><creatorcontrib>Kato, Akihiko</creatorcontrib><creatorcontrib>Miyajima, Hiroaki</creatorcontrib><creatorcontrib>Yasuda, Hideo</creatorcontrib><title>The Relationship between the Intrarenal Dopamine System and Intrarenal Renin-angiotensin System Depending on the Renal Function</title><title>Internal Medicine</title><addtitle>Intern. Med.</addtitle><description>Objective The mechanisms underlying the intrarenal renin-angiotensin system (RAS) activation depend on the conditions of kidney diseases. In angiotensin II (AngII) infusion models, the circulating AngII is filtered into the renal tubular lumens, activating intrarenal RAS. However, in the chronic kidney disease (CKD) models, plasma angiotensinogen (AGT) is filtered into the tubular lumens because of glomerular injury, activating intrarenal RAS. The intrarenal dopamine system activation reduces intrarenal AGT expression and suppresses the intrarenal RAS activity in AngII infusion models. However, the relationship between the intrarenal dopamine system and intrarenal RAS has not been elucidated. Therefore, this study was conducted to determine that relationship in CKD patients. Methods We recruited 46 CKD patients (age: 51.1±20.0 years; 16 men; causes of CKD: chronic glomerulonephritis, 34; diabetic nephropathy, 2; nephrosclerosis, 4; and others, 6) not undergoing dialysis or taking RAS blockers. The urinary dopamine (U-DOPA) level, an indicator of intrarenal dopamine activity, and the urinary AGT (U-AGT) level, a surrogate marker of intrarenal RAS activity, were measured. Results As the CKD stages progressed, the U-DOPA levels decreased while the U-AGT levels increased. The U-DOPA levels were significantly and negatively correlated with the U-AGT levels but significantly and positively correlated with the estimated glomerular filtration rate (eGFR). A multiple regression analysis revealed that the U-DOPA levels were associated with the U-AGT levels after adjusting for age, sex, body mass index, and blood pressure (β=-0.38, p=0.045). However, no correlation was observed when eGFR was also adjusted (β=-0.17, p=0.29). Conclusion The negative correlation between the intrarenal dopamine system and intrarenal RAS in CKD patients may be affected by the renal function.</description><subject>Activation</subject><subject>Adult</subject><subject>Angiotensin</subject><subject>Angiotensin II</subject><subject>Angiotensinogen</subject><subject>Blood pressure</subject><subject>Body mass</subject><subject>Body mass index</subject><subject>Diabetes mellitus</subject><subject>Dialysis</subject><subject>Dihydroxyphenylalanine</subject><subject>Dopamine</subject><subject>Dopamine - metabolism</subject><subject>Epidermal growth factor receptors</subject><subject>Female</subject><subject>Glomerular filtration rate</subject><subject>Glomerular Filtration Rate - physiology</subject><subject>Glomerulonephritis</subject><subject>Humans</subject><subject>Internal medicine</subject><subject>intrarenal dopamine system</subject><subject>kidney</subject><subject>Kidney - metabolism</subject><subject>Kidney - physiopathology</subject><subject>Kidney diseases</subject><subject>Kidneys</subject><subject>Lumens</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Multiple regression analysis</subject><subject>Nephropathy</subject><subject>Original</subject><subject>Renal function</subject><subject>Renal Insufficiency, Chronic - metabolism</subject><subject>Renal Insufficiency, Chronic - physiopathology</subject><subject>Renin</subject><subject>renin-angiotensin system</subject><subject>Renin-Angiotensin System - physiology</subject><subject>urinary angiotensinogen</subject><issn>0918-2918</issn><issn>1349-7235</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNplkU9v1DAQxS0EokvhK6BIXLik2E7iPxck1NJSqVKlpZwtx5nsepXYwXZAPfHV67DbVSmX8WF-8-Z5HkIFwWeUMPnJugTB6WGEzhrr4AxLWZdEvEArUtWy5LRqXqIVlkSUNJcT9CbGHcaV4JK-RidUSlFzLlfoz90WijUMOlnv4tZORQvpN4ArUm5cuxR0gLypuPCTHvOq4vt9TDAW2nVP22tw1pXabaxP4KJ1j9wFTOA66zaF32uu__KXszPLyrfoVa-HCO8O7yn6cfn17vxbeXN7dX3-5aY0jPFUCtKTTkDL-0rWXcO4wbTtRGM066BvqdA91JTm4wCuW-hISzHgPNATjvtGVqfo8153mtt8NQOL9UFNwY463Cuvrfq34-xWbfwvxWi-maizwMeDQPA_Z4hJjTYaGAbtwM9RUcw4qbIBnNEPz9Cdn5e4MkVrJln2QzMl9pQJPsYA_dEMwWpJWT1PWS0pKyLy6PunnzkOPsaagds9sItJb-AI6JCsGeB_5YZna0s9rDiSZquDAlc9AJ_ByfY</recordid><startdate>20181115</startdate><enddate>20181115</enddate><creator>Matsuyama, Takashi</creator><creator>Ohashi, Naro</creator><creator>Ishigaki, Sayaka</creator><creator>Isobe, Shinsuke</creator><creator>Tsuji, Naoko</creator><creator>Fujikura, Tomoyuki</creator><creator>Tsuji, Takayuki</creator><creator>Kato, Akihiko</creator><creator>Miyajima, Hiroaki</creator><creator>Yasuda, Hideo</creator><general>The Japanese Society of Internal Medicine</general><general>Japan Science and Technology Agency</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>7T5</scope><scope>7TK</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20181115</creationdate><title>The Relationship between the Intrarenal Dopamine System and Intrarenal Renin-angiotensin System Depending on the Renal Function</title><author>Matsuyama, Takashi ; Ohashi, Naro ; Ishigaki, Sayaka ; Isobe, Shinsuke ; Tsuji, Naoko ; Fujikura, Tomoyuki ; Tsuji, Takayuki ; Kato, Akihiko ; Miyajima, Hiroaki ; Yasuda, Hideo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c667t-81f1d8eb7f394d567c02bd85ca6defb28afe422216e04bed1b20e08ebf170f593</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Activation</topic><topic>Adult</topic><topic>Angiotensin</topic><topic>Angiotensin II</topic><topic>Angiotensinogen</topic><topic>Blood pressure</topic><topic>Body mass</topic><topic>Body mass index</topic><topic>Diabetes mellitus</topic><topic>Dialysis</topic><topic>Dihydroxyphenylalanine</topic><topic>Dopamine</topic><topic>Dopamine - metabolism</topic><topic>Epidermal growth factor receptors</topic><topic>Female</topic><topic>Glomerular filtration rate</topic><topic>Glomerular Filtration Rate - physiology</topic><topic>Glomerulonephritis</topic><topic>Humans</topic><topic>Internal medicine</topic><topic>intrarenal dopamine system</topic><topic>kidney</topic><topic>Kidney - metabolism</topic><topic>Kidney - physiopathology</topic><topic>Kidney diseases</topic><topic>Kidneys</topic><topic>Lumens</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Multiple regression analysis</topic><topic>Nephropathy</topic><topic>Original</topic><topic>Renal function</topic><topic>Renal Insufficiency, Chronic - metabolism</topic><topic>Renal Insufficiency, Chronic - physiopathology</topic><topic>Renin</topic><topic>renin-angiotensin system</topic><topic>Renin-Angiotensin System - physiology</topic><topic>urinary angiotensinogen</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Matsuyama, Takashi</creatorcontrib><creatorcontrib>Ohashi, Naro</creatorcontrib><creatorcontrib>Ishigaki, Sayaka</creatorcontrib><creatorcontrib>Isobe, Shinsuke</creatorcontrib><creatorcontrib>Tsuji, Naoko</creatorcontrib><creatorcontrib>Fujikura, Tomoyuki</creatorcontrib><creatorcontrib>Tsuji, Takayuki</creatorcontrib><creatorcontrib>Kato, Akihiko</creatorcontrib><creatorcontrib>Miyajima, Hiroaki</creatorcontrib><creatorcontrib>Yasuda, Hideo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Internal Medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Matsuyama, Takashi</au><au>Ohashi, Naro</au><au>Ishigaki, Sayaka</au><au>Isobe, Shinsuke</au><au>Tsuji, Naoko</au><au>Fujikura, Tomoyuki</au><au>Tsuji, Takayuki</au><au>Kato, Akihiko</au><au>Miyajima, Hiroaki</au><au>Yasuda, Hideo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Relationship between the Intrarenal Dopamine System and Intrarenal Renin-angiotensin System Depending on the Renal Function</atitle><jtitle>Internal Medicine</jtitle><addtitle>Intern. Med.</addtitle><date>2018-11-15</date><risdate>2018</risdate><volume>57</volume><issue>22</issue><spage>3241</spage><epage>3247</epage><pages>3241-3247</pages><issn>0918-2918</issn><eissn>1349-7235</eissn><abstract>Objective The mechanisms underlying the intrarenal renin-angiotensin system (RAS) activation depend on the conditions of kidney diseases. In angiotensin II (AngII) infusion models, the circulating AngII is filtered into the renal tubular lumens, activating intrarenal RAS. However, in the chronic kidney disease (CKD) models, plasma angiotensinogen (AGT) is filtered into the tubular lumens because of glomerular injury, activating intrarenal RAS. The intrarenal dopamine system activation reduces intrarenal AGT expression and suppresses the intrarenal RAS activity in AngII infusion models. However, the relationship between the intrarenal dopamine system and intrarenal RAS has not been elucidated. Therefore, this study was conducted to determine that relationship in CKD patients. Methods We recruited 46 CKD patients (age: 51.1±20.0 years; 16 men; causes of CKD: chronic glomerulonephritis, 34; diabetic nephropathy, 2; nephrosclerosis, 4; and others, 6) not undergoing dialysis or taking RAS blockers. The urinary dopamine (U-DOPA) level, an indicator of intrarenal dopamine activity, and the urinary AGT (U-AGT) level, a surrogate marker of intrarenal RAS activity, were measured. Results As the CKD stages progressed, the U-DOPA levels decreased while the U-AGT levels increased. The U-DOPA levels were significantly and negatively correlated with the U-AGT levels but significantly and positively correlated with the estimated glomerular filtration rate (eGFR). A multiple regression analysis revealed that the U-DOPA levels were associated with the U-AGT levels after adjusting for age, sex, body mass index, and blood pressure (β=-0.38, p=0.045). However, no correlation was observed when eGFR was also adjusted (β=-0.17, p=0.29). Conclusion The negative correlation between the intrarenal dopamine system and intrarenal RAS in CKD patients may be affected by the renal function.</abstract><cop>Japan</cop><pub>The Japanese Society of Internal Medicine</pub><pmid>29984779</pmid><doi>10.2169/internalmedicine.0994-18</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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1349-7235
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subjects Activation
Adult
Angiotensin
Angiotensin II
Angiotensinogen
Blood pressure
Body mass
Body mass index
Diabetes mellitus
Dialysis
Dihydroxyphenylalanine
Dopamine
Dopamine - metabolism
Epidermal growth factor receptors
Female
Glomerular filtration rate
Glomerular Filtration Rate - physiology
Glomerulonephritis
Humans
Internal medicine
intrarenal dopamine system
kidney
Kidney - metabolism
Kidney - physiopathology
Kidney diseases
Kidneys
Lumens
Male
Middle Aged
Multiple regression analysis
Nephropathy
Original
Renal function
Renal Insufficiency, Chronic - metabolism
Renal Insufficiency, Chronic - physiopathology
Renin
renin-angiotensin system
Renin-Angiotensin System - physiology
urinary angiotensinogen
title The Relationship between the Intrarenal Dopamine System and Intrarenal Renin-angiotensin System Depending on the Renal Function
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