The selective mineralocorticoid receptor modulator AZD9977 reveals differences in mineralocorticoid effects of aldosterone and fludrocortisone
Introduction: AZD9977 is a novel mineralocorticoid receptor (MR) modulator, which in preclinical studies demonstrated organ protection without affecting aldosterone-regulated urinary electrolyte excretion. However, when tested in humans, using fludrocortisone as an MR agonist, AZD9977 exhibited simi...
Gespeichert in:
| Veröffentlicht in: | Journal of the renin-angiotensin-aldosterone system 2019-01, Vol.20 (1), p.1470320319827449-1470320319827449 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1470320319827449 |
|---|---|
| container_issue | 1 |
| container_start_page | 1470320319827449 |
| container_title | Journal of the renin-angiotensin-aldosterone system |
| container_volume | 20 |
| creator | Bamberg, Krister William-Olsson, Lena Johansson, Ulrika Jansson-Löfmark, Rasmus Hartleib-Geschwindner, Judith |
| description | Introduction:
AZD9977 is a novel mineralocorticoid receptor (MR) modulator, which in preclinical studies demonstrated organ protection without affecting aldosterone-regulated urinary electrolyte excretion. However, when tested in humans, using fludrocortisone as an MR agonist, AZD9977 exhibited similar effects on urinary Na+/K+ ratio as eplerenone. The aim of this study is to understand whether the contradictory results seen in rats and humans are due to the mineralocorticoid used.
Materials and methods:
Rats were treated with single doses of AZD9977 or eplerenone in combination with either aldosterone or fludrocortisone. Urine was collected for five to six hours and total amounts excreted Na+ and K+ were assessed.
Results:
AZD9977 dose-dependently increased urinary Na+/K+ ratio in rats when tested against fludrocortisone, but not when tested against aldosterone. Eplerenone dose-dependently increased urinary Na+/K+ ratio when tested against fludrocortisone as well as aldosterone.
Conclusions:
The data suggest that the contrasting effects of AZD9977 on urinary electrolyte excretion observed in rats and humans are due to the use of the synthetic mineralocorticoid fludrocortisone. Future clinical studies are required to confirm the reduced electrolyte effects of AZD9977 and the subsequent lower predicted hyperkalemia risk. |
| doi_str_mv | 10.1177/1470320319827449 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6396052</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1177_1470320319827449</sage_id><sourcerecordid>2315081144</sourcerecordid><originalsourceid>FETCH-LOGICAL-c462t-8f3969cd6a39dc38cb83a726ded970cff581f57e00b6a8d530eb1d1f625479b73</originalsourceid><addsrcrecordid>eNp1kU1rFTEUhoMottbuXUnAjZvRfM0k2QilfkKhm7pxEzLJSZsyk1yTmQv9E_5mc7m11WJXOeR9znvO4UXoFSXvKJXyPRWScEY41YpJIfQTdEhlzzql5fC01U3udvoBelHrNSFcCcGeowNOFOWK00P06-IKcIUJ3BK3gOeYoNgpu1yW6HL0uICDzZILnrNfJ7urTn581FrKJm3BThX7GAIUSA4qjuk_HtB0t1ScA7aTz3WBkhNgmzwO0-rLHq3t7yV6FpolHN--R-j7508Xp1-7s_Mv305PzjonBrZ0KnA9aOcHy7V3XLlRcSvZ4MFrSVwIvaKhl0DIOFjle05gpJ6GgfVC6lHyI_Rh77tZxxm8g7S0lc2mxNmWG5NtNP8qKV6Zy7w1QxtMetYM3t4alPxzhbqYOVYH02QT5LUaRpUkjPeSN_TNA_Q6ryW18wzjtG9RUCEaRfaUK7nWAuFuGUrMLmzzMOzW8vrvI-4a_qTbgG4PVHsJ91MfNfwNEBC1bg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2315081144</pqid></control><display><type>article</type><title>The selective mineralocorticoid receptor modulator AZD9977 reveals differences in mineralocorticoid effects of aldosterone and fludrocortisone</title><source>PubMed Central</source><source>EZB Electronic Journals Library</source><source>PubMed Central Open Access</source><creator>Bamberg, Krister ; William-Olsson, Lena ; Johansson, Ulrika ; Jansson-Löfmark, Rasmus ; Hartleib-Geschwindner, Judith</creator><creatorcontrib>Bamberg, Krister ; William-Olsson, Lena ; Johansson, Ulrika ; Jansson-Löfmark, Rasmus ; Hartleib-Geschwindner, Judith</creatorcontrib><description>Introduction:
AZD9977 is a novel mineralocorticoid receptor (MR) modulator, which in preclinical studies demonstrated organ protection without affecting aldosterone-regulated urinary electrolyte excretion. However, when tested in humans, using fludrocortisone as an MR agonist, AZD9977 exhibited similar effects on urinary Na+/K+ ratio as eplerenone. The aim of this study is to understand whether the contradictory results seen in rats and humans are due to the mineralocorticoid used.
Materials and methods:
Rats were treated with single doses of AZD9977 or eplerenone in combination with either aldosterone or fludrocortisone. Urine was collected for five to six hours and total amounts excreted Na+ and K+ were assessed.
Results:
AZD9977 dose-dependently increased urinary Na+/K+ ratio in rats when tested against fludrocortisone, but not when tested against aldosterone. Eplerenone dose-dependently increased urinary Na+/K+ ratio when tested against fludrocortisone as well as aldosterone.
Conclusions:
The data suggest that the contrasting effects of AZD9977 on urinary electrolyte excretion observed in rats and humans are due to the use of the synthetic mineralocorticoid fludrocortisone. Future clinical studies are required to confirm the reduced electrolyte effects of AZD9977 and the subsequent lower predicted hyperkalemia risk.</description><identifier>ISSN: 1470-3203</identifier><identifier>EISSN: 1752-8976</identifier><identifier>DOI: 10.1177/1470320319827449</identifier><identifier>PMID: 30813831</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Electrolytes ; Short Communication ; Sodium</subject><ispartof>Journal of the renin-angiotensin-aldosterone system, 2019-01, Vol.20 (1), p.1470320319827449-1470320319827449</ispartof><rights>The Author(s) 2019</rights><rights>The Author(s) 2019. This work is licensed under the Creative Commons Attribution – Non-Commercial License http://www.creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2019 2019 SAGE Publications</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c462t-8f3969cd6a39dc38cb83a726ded970cff581f57e00b6a8d530eb1d1f625479b73</citedby><cites>FETCH-LOGICAL-c462t-8f3969cd6a39dc38cb83a726ded970cff581f57e00b6a8d530eb1d1f625479b73</cites><orcidid>0000-0002-0538-6083</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396052/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396052/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30813831$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bamberg, Krister</creatorcontrib><creatorcontrib>William-Olsson, Lena</creatorcontrib><creatorcontrib>Johansson, Ulrika</creatorcontrib><creatorcontrib>Jansson-Löfmark, Rasmus</creatorcontrib><creatorcontrib>Hartleib-Geschwindner, Judith</creatorcontrib><title>The selective mineralocorticoid receptor modulator AZD9977 reveals differences in mineralocorticoid effects of aldosterone and fludrocortisone</title><title>Journal of the renin-angiotensin-aldosterone system</title><addtitle>J Renin Angiotensin Aldosterone Syst</addtitle><description>Introduction:
AZD9977 is a novel mineralocorticoid receptor (MR) modulator, which in preclinical studies demonstrated organ protection without affecting aldosterone-regulated urinary electrolyte excretion. However, when tested in humans, using fludrocortisone as an MR agonist, AZD9977 exhibited similar effects on urinary Na+/K+ ratio as eplerenone. The aim of this study is to understand whether the contradictory results seen in rats and humans are due to the mineralocorticoid used.
Materials and methods:
Rats were treated with single doses of AZD9977 or eplerenone in combination with either aldosterone or fludrocortisone. Urine was collected for five to six hours and total amounts excreted Na+ and K+ were assessed.
Results:
AZD9977 dose-dependently increased urinary Na+/K+ ratio in rats when tested against fludrocortisone, but not when tested against aldosterone. Eplerenone dose-dependently increased urinary Na+/K+ ratio when tested against fludrocortisone as well as aldosterone.
Conclusions:
The data suggest that the contrasting effects of AZD9977 on urinary electrolyte excretion observed in rats and humans are due to the use of the synthetic mineralocorticoid fludrocortisone. Future clinical studies are required to confirm the reduced electrolyte effects of AZD9977 and the subsequent lower predicted hyperkalemia risk.</description><subject>Electrolytes</subject><subject>Short Communication</subject><subject>Sodium</subject><issn>1470-3203</issn><issn>1752-8976</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>AFRWT</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kU1rFTEUhoMottbuXUnAjZvRfM0k2QilfkKhm7pxEzLJSZsyk1yTmQv9E_5mc7m11WJXOeR9znvO4UXoFSXvKJXyPRWScEY41YpJIfQTdEhlzzql5fC01U3udvoBelHrNSFcCcGeowNOFOWK00P06-IKcIUJ3BK3gOeYoNgpu1yW6HL0uICDzZILnrNfJ7urTn581FrKJm3BThX7GAIUSA4qjuk_HtB0t1ScA7aTz3WBkhNgmzwO0-rLHq3t7yV6FpolHN--R-j7508Xp1-7s_Mv305PzjonBrZ0KnA9aOcHy7V3XLlRcSvZ4MFrSVwIvaKhl0DIOFjle05gpJ6GgfVC6lHyI_Rh77tZxxm8g7S0lc2mxNmWG5NtNP8qKV6Zy7w1QxtMetYM3t4alPxzhbqYOVYH02QT5LUaRpUkjPeSN_TNA_Q6ryW18wzjtG9RUCEaRfaUK7nWAuFuGUrMLmzzMOzW8vrvI-4a_qTbgG4PVHsJ91MfNfwNEBC1bg</recordid><startdate>20190101</startdate><enddate>20190101</enddate><creator>Bamberg, Krister</creator><creator>William-Olsson, Lena</creator><creator>Johansson, Ulrika</creator><creator>Jansson-Löfmark, Rasmus</creator><creator>Hartleib-Geschwindner, Judith</creator><general>SAGE Publications</general><general>Hindawi Limited</general><scope>AFRWT</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>NAPCQ</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0538-6083</orcidid></search><sort><creationdate>20190101</creationdate><title>The selective mineralocorticoid receptor modulator AZD9977 reveals differences in mineralocorticoid effects of aldosterone and fludrocortisone</title><author>Bamberg, Krister ; William-Olsson, Lena ; Johansson, Ulrika ; Jansson-Löfmark, Rasmus ; Hartleib-Geschwindner, Judith</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c462t-8f3969cd6a39dc38cb83a726ded970cff581f57e00b6a8d530eb1d1f625479b73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Electrolytes</topic><topic>Short Communication</topic><topic>Sodium</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bamberg, Krister</creatorcontrib><creatorcontrib>William-Olsson, Lena</creatorcontrib><creatorcontrib>Johansson, Ulrika</creatorcontrib><creatorcontrib>Jansson-Löfmark, Rasmus</creatorcontrib><creatorcontrib>Hartleib-Geschwindner, Judith</creatorcontrib><collection>SAGE Journals Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database (ProQuest)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Nursing & Allied Health Premium</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of the renin-angiotensin-aldosterone system</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bamberg, Krister</au><au>William-Olsson, Lena</au><au>Johansson, Ulrika</au><au>Jansson-Löfmark, Rasmus</au><au>Hartleib-Geschwindner, Judith</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The selective mineralocorticoid receptor modulator AZD9977 reveals differences in mineralocorticoid effects of aldosterone and fludrocortisone</atitle><jtitle>Journal of the renin-angiotensin-aldosterone system</jtitle><addtitle>J Renin Angiotensin Aldosterone Syst</addtitle><date>2019-01-01</date><risdate>2019</risdate><volume>20</volume><issue>1</issue><spage>1470320319827449</spage><epage>1470320319827449</epage><pages>1470320319827449-1470320319827449</pages><issn>1470-3203</issn><eissn>1752-8976</eissn><abstract>Introduction:
AZD9977 is a novel mineralocorticoid receptor (MR) modulator, which in preclinical studies demonstrated organ protection without affecting aldosterone-regulated urinary electrolyte excretion. However, when tested in humans, using fludrocortisone as an MR agonist, AZD9977 exhibited similar effects on urinary Na+/K+ ratio as eplerenone. The aim of this study is to understand whether the contradictory results seen in rats and humans are due to the mineralocorticoid used.
Materials and methods:
Rats were treated with single doses of AZD9977 or eplerenone in combination with either aldosterone or fludrocortisone. Urine was collected for five to six hours and total amounts excreted Na+ and K+ were assessed.
Results:
AZD9977 dose-dependently increased urinary Na+/K+ ratio in rats when tested against fludrocortisone, but not when tested against aldosterone. Eplerenone dose-dependently increased urinary Na+/K+ ratio when tested against fludrocortisone as well as aldosterone.
Conclusions:
The data suggest that the contrasting effects of AZD9977 on urinary electrolyte excretion observed in rats and humans are due to the use of the synthetic mineralocorticoid fludrocortisone. Future clinical studies are required to confirm the reduced electrolyte effects of AZD9977 and the subsequent lower predicted hyperkalemia risk.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>30813831</pmid><doi>10.1177/1470320319827449</doi><orcidid>https://orcid.org/0000-0002-0538-6083</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1470-3203 |
| ispartof | Journal of the renin-angiotensin-aldosterone system, 2019-01, Vol.20 (1), p.1470320319827449-1470320319827449 |
| issn | 1470-3203 1752-8976 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6396052 |
| source | PubMed Central; EZB Electronic Journals Library; PubMed Central Open Access |
| subjects | Electrolytes Short Communication Sodium |
| title | The selective mineralocorticoid receptor modulator AZD9977 reveals differences in mineralocorticoid effects of aldosterone and fludrocortisone |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T17%3A00%3A20IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20selective%20mineralocorticoid%20receptor%20modulator%20AZD9977%20reveals%20differences%20in%20mineralocorticoid%20effects%20of%20aldosterone%20and%20fludrocortisone&rft.jtitle=Journal%20of%20the%20renin-angiotensin-aldosterone%20system&rft.au=Bamberg,%20Krister&rft.date=2019-01-01&rft.volume=20&rft.issue=1&rft.spage=1470320319827449&rft.epage=1470320319827449&rft.pages=1470320319827449-1470320319827449&rft.issn=1470-3203&rft.eissn=1752-8976&rft_id=info:doi/10.1177/1470320319827449&rft_dat=%3Cproquest_pubme%3E2315081144%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2315081144&rft_id=info:pmid/30813831&rft_sage_id=10.1177_1470320319827449&rfr_iscdi=true |