Differential restoration of functional hyperemia by antihypertensive drug classes in hypertension-related cerebral small vessel disease
Dementia resulting from small vessel diseases (SVDs) of the brain is an emerging epidemic for which there is no treatment. Hypertension is the major risk factor for SVDs, but how hypertension damages the brain microcirculation is unclear. Here, we show that chronic hypertension in a mouse model prog...
Gespeichert in:
| Veröffentlicht in: | The Journal of clinical investigation 2021-09, Vol.131 (18) |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 18 |
| container_start_page | |
| container_title | The Journal of clinical investigation |
| container_volume | 131 |
| creator | Koide, Masayo Harraz, Osama F Dabertrand, Fabrice Longden, Thomas A Ferris, Hannah R Wellman, George C Hill-Eubanks, David C Greenstein, Adam S Nelson, Mark T |
| description | Dementia resulting from small vessel diseases (SVDs) of the brain is an emerging epidemic for which there is no treatment. Hypertension is the major risk factor for SVDs, but how hypertension damages the brain microcirculation is unclear. Here, we show that chronic hypertension in a mouse model progressively disrupts on-demand delivery of blood to metabolically active areas of the brain (functional hyperemia) through diminished activity of the capillary endothelial cell inward-rectifier potassium channel, Kir2.1. Despite similar efficacy in reducing blood pressure, amlodipine, a voltage-dependent calcium-channel blocker, prevented hypertension-related damage to functional hyperemia whereas losartan, an angiotensin II type 1 receptor blocker, did not. We attribute this drug class effect to losartan-induced aldosterone breakthrough, a phenomenon triggered by pharmacological interruption of the renin-angiotensin pathway leading to elevated plasma aldosterone levels. This hypothesis is supported by the finding that combining losartan with the aldosterone receptor antagonist eplerenone prevented the hypertension-related decline in functional hyperemia. Collectively, these data suggest Kir2.1 as a possible therapeutic target in vascular dementia and indicate that concurrent mineralocorticoid aldosterone receptor blockade may aid in protecting against late-life cognitive decline in hypertensive patients treated with angiotensin II type 1 receptor blockers. |
| doi_str_mv | 10.1172/JCI149029 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8439604</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A677401844</galeid><sourcerecordid>A677401844</sourcerecordid><originalsourceid>FETCH-LOGICAL-c619t-1e221a27a2b8bd577651b1c210114d42517fefc6841a2a9474936c58787220c53</originalsourceid><addsrcrecordid>eNqN0luL1DAUB_AiinvRB7-ABARZH7o2adKkL8Iy3kYWFry9hjQ97UTSZDZpB-cT-LVN3XWcgXmQPjTk_PJPm5wse4aLS4w5ef1pscS0Lkj9IDvFjIlckFI83BufZGcx_igKTCmjj7OTkpYMC16cZr_emq6DAG40yqIAcfRBjcY75DvUTU7P41RZbddJDUahZotU0n8mRnDRbAC1YeqRtipGiMg49K_oXR7AqhFapFNAE1JWHJS1aANJW9SaCCrCk-xRp2yEp_fv8-zb-3dfFx_z65sPy8XVda4rXI85BkKwIlyRRjQt47xiuMGa4AJj2lLCMO-g05WgSamaclqXlWaCC05IoVl5nr25y11PzQCtTj-ePkmugxlU2EqvjDysOLOSvd9IQcu6KmgKuLgPCP52SuclBxM1WKsc-ClKwlhNy4qTmb64o72yII3rfErUM5dXFee0wILOKj-ienCQtvcOOpOmD_zlEZ-eNl2PPrrg1cGCZEb4OfZqilEuv3z-f3vz_dC-3LMrUHZcRW-nuWPi0VAdfIwBut1x40LODSx3DZzs8_372cm_HVv-BoYY6gs</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2559436724</pqid></control><display><type>article</type><title>Differential restoration of functional hyperemia by antihypertensive drug classes in hypertension-related cerebral small vessel disease</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Koide, Masayo ; Harraz, Osama F ; Dabertrand, Fabrice ; Longden, Thomas A ; Ferris, Hannah R ; Wellman, George C ; Hill-Eubanks, David C ; Greenstein, Adam S ; Nelson, Mark T</creator><creatorcontrib>Koide, Masayo ; Harraz, Osama F ; Dabertrand, Fabrice ; Longden, Thomas A ; Ferris, Hannah R ; Wellman, George C ; Hill-Eubanks, David C ; Greenstein, Adam S ; Nelson, Mark T</creatorcontrib><description>Dementia resulting from small vessel diseases (SVDs) of the brain is an emerging epidemic for which there is no treatment. Hypertension is the major risk factor for SVDs, but how hypertension damages the brain microcirculation is unclear. Here, we show that chronic hypertension in a mouse model progressively disrupts on-demand delivery of blood to metabolically active areas of the brain (functional hyperemia) through diminished activity of the capillary endothelial cell inward-rectifier potassium channel, Kir2.1. Despite similar efficacy in reducing blood pressure, amlodipine, a voltage-dependent calcium-channel blocker, prevented hypertension-related damage to functional hyperemia whereas losartan, an angiotensin II type 1 receptor blocker, did not. We attribute this drug class effect to losartan-induced aldosterone breakthrough, a phenomenon triggered by pharmacological interruption of the renin-angiotensin pathway leading to elevated plasma aldosterone levels. This hypothesis is supported by the finding that combining losartan with the aldosterone receptor antagonist eplerenone prevented the hypertension-related decline in functional hyperemia. Collectively, these data suggest Kir2.1 as a possible therapeutic target in vascular dementia and indicate that concurrent mineralocorticoid aldosterone receptor blockade may aid in protecting against late-life cognitive decline in hypertensive patients treated with angiotensin II type 1 receptor blockers.</description><identifier>ISSN: 1558-8238</identifier><identifier>ISSN: 0021-9738</identifier><identifier>EISSN: 1558-8238</identifier><identifier>DOI: 10.1172/JCI149029</identifier><identifier>PMID: 34351870</identifier><language>eng</language><publisher>United States: American Society for Clinical Investigation</publisher><subject>Amlodipine - therapeutic use ; Angiotensin II Type 1 Receptor Blockers - administration & dosage ; Angiotensin II Type 1 Receptor Blockers - therapeutic use ; Animals ; Antihypertensive Agents - administration & dosage ; Antihypertensive Agents - therapeutic use ; Antihypertensive drugs ; Blood circulation ; Cerebral Small Vessel Diseases - drug therapy ; Cerebral Small Vessel Diseases - etiology ; Cerebral Small Vessel Diseases - physiopathology ; Cerebrovascular Circulation - drug effects ; Cerebrovascular Circulation - physiology ; Cerebrovascular disease ; Complications and side effects ; Concise Communication ; Dementia, Vascular - drug therapy ; Dementia, Vascular - etiology ; Dementia, Vascular - physiopathology ; Disease Models, Animal ; Drug therapy ; Drug Therapy, Combination ; Eplerenone - administration & dosage ; Eplerenone - therapeutic use ; Health aspects ; Heart Disease Risk Factors ; Humans ; Hyperemia - drug therapy ; Hyperemia - physiopathology ; Hypertension ; Hypertension - complications ; Hypertension - drug therapy ; Losartan - administration & dosage ; Losartan - therapeutic use ; Male ; Mice ; Microvessels - drug effects ; Microvessels - physiopathology ; Pharmacology, Experimental ; Potassium Channels, Inwardly Rectifying - drug effects ; Potassium Channels, Inwardly Rectifying - physiology ; Renin-Angiotensin System - drug effects ; Renin-Angiotensin System - physiology</subject><ispartof>The Journal of clinical investigation, 2021-09, Vol.131 (18)</ispartof><rights>COPYRIGHT 2021 American Society for Clinical Investigation</rights><rights>2021 American Society for Clinical Investigation 2021 American Society for Clinical Investigation</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c619t-1e221a27a2b8bd577651b1c210114d42517fefc6841a2a9474936c58787220c53</citedby><cites>FETCH-LOGICAL-c619t-1e221a27a2b8bd577651b1c210114d42517fefc6841a2a9474936c58787220c53</cites><orcidid>0000-0003-2541-9185 ; 0000-0003-2061-1100 ; 0000-0002-7950-7677</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/PMC8439604/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439604/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34351870$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Koide, Masayo</creatorcontrib><creatorcontrib>Harraz, Osama F</creatorcontrib><creatorcontrib>Dabertrand, Fabrice</creatorcontrib><creatorcontrib>Longden, Thomas A</creatorcontrib><creatorcontrib>Ferris, Hannah R</creatorcontrib><creatorcontrib>Wellman, George C</creatorcontrib><creatorcontrib>Hill-Eubanks, David C</creatorcontrib><creatorcontrib>Greenstein, Adam S</creatorcontrib><creatorcontrib>Nelson, Mark T</creatorcontrib><title>Differential restoration of functional hyperemia by antihypertensive drug classes in hypertension-related cerebral small vessel disease</title><title>The Journal of clinical investigation</title><addtitle>J Clin Invest</addtitle><description>Dementia resulting from small vessel diseases (SVDs) of the brain is an emerging epidemic for which there is no treatment. Hypertension is the major risk factor for SVDs, but how hypertension damages the brain microcirculation is unclear. Here, we show that chronic hypertension in a mouse model progressively disrupts on-demand delivery of blood to metabolically active areas of the brain (functional hyperemia) through diminished activity of the capillary endothelial cell inward-rectifier potassium channel, Kir2.1. Despite similar efficacy in reducing blood pressure, amlodipine, a voltage-dependent calcium-channel blocker, prevented hypertension-related damage to functional hyperemia whereas losartan, an angiotensin II type 1 receptor blocker, did not. We attribute this drug class effect to losartan-induced aldosterone breakthrough, a phenomenon triggered by pharmacological interruption of the renin-angiotensin pathway leading to elevated plasma aldosterone levels. This hypothesis is supported by the finding that combining losartan with the aldosterone receptor antagonist eplerenone prevented the hypertension-related decline in functional hyperemia. Collectively, these data suggest Kir2.1 as a possible therapeutic target in vascular dementia and indicate that concurrent mineralocorticoid aldosterone receptor blockade may aid in protecting against late-life cognitive decline in hypertensive patients treated with angiotensin II type 1 receptor blockers.</description><subject>Amlodipine - therapeutic use</subject><subject>Angiotensin II Type 1 Receptor Blockers - administration & dosage</subject><subject>Angiotensin II Type 1 Receptor Blockers - therapeutic use</subject><subject>Animals</subject><subject>Antihypertensive Agents - administration & dosage</subject><subject>Antihypertensive Agents - therapeutic use</subject><subject>Antihypertensive drugs</subject><subject>Blood circulation</subject><subject>Cerebral Small Vessel Diseases - drug therapy</subject><subject>Cerebral Small Vessel Diseases - etiology</subject><subject>Cerebral Small Vessel Diseases - physiopathology</subject><subject>Cerebrovascular Circulation - drug effects</subject><subject>Cerebrovascular Circulation - physiology</subject><subject>Cerebrovascular disease</subject><subject>Complications and side effects</subject><subject>Concise Communication</subject><subject>Dementia, Vascular - drug therapy</subject><subject>Dementia, Vascular - etiology</subject><subject>Dementia, Vascular - physiopathology</subject><subject>Disease Models, Animal</subject><subject>Drug therapy</subject><subject>Drug Therapy, Combination</subject><subject>Eplerenone - administration & dosage</subject><subject>Eplerenone - therapeutic use</subject><subject>Health aspects</subject><subject>Heart Disease Risk Factors</subject><subject>Humans</subject><subject>Hyperemia - drug therapy</subject><subject>Hyperemia - physiopathology</subject><subject>Hypertension</subject><subject>Hypertension - complications</subject><subject>Hypertension - drug therapy</subject><subject>Losartan - administration & dosage</subject><subject>Losartan - therapeutic use</subject><subject>Male</subject><subject>Mice</subject><subject>Microvessels - drug effects</subject><subject>Microvessels - physiopathology</subject><subject>Pharmacology, Experimental</subject><subject>Potassium Channels, Inwardly Rectifying - drug effects</subject><subject>Potassium Channels, Inwardly Rectifying - physiology</subject><subject>Renin-Angiotensin System - drug effects</subject><subject>Renin-Angiotensin System - physiology</subject><issn>1558-8238</issn><issn>0021-9738</issn><issn>1558-8238</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0luL1DAUB_AiinvRB7-ABARZH7o2adKkL8Iy3kYWFry9hjQ97UTSZDZpB-cT-LVN3XWcgXmQPjTk_PJPm5wse4aLS4w5ef1pscS0Lkj9IDvFjIlckFI83BufZGcx_igKTCmjj7OTkpYMC16cZr_emq6DAG40yqIAcfRBjcY75DvUTU7P41RZbddJDUahZotU0n8mRnDRbAC1YeqRtipGiMg49K_oXR7AqhFapFNAE1JWHJS1aANJW9SaCCrCk-xRp2yEp_fv8-zb-3dfFx_z65sPy8XVda4rXI85BkKwIlyRRjQt47xiuMGa4AJj2lLCMO-g05WgSamaclqXlWaCC05IoVl5nr25y11PzQCtTj-ePkmugxlU2EqvjDysOLOSvd9IQcu6KmgKuLgPCP52SuclBxM1WKsc-ClKwlhNy4qTmb64o72yII3rfErUM5dXFee0wILOKj-ienCQtvcOOpOmD_zlEZ-eNl2PPrrg1cGCZEb4OfZqilEuv3z-f3vz_dC-3LMrUHZcRW-nuWPi0VAdfIwBut1x40LODSx3DZzs8_372cm_HVv-BoYY6gs</recordid><startdate>20210915</startdate><enddate>20210915</enddate><creator>Koide, Masayo</creator><creator>Harraz, Osama F</creator><creator>Dabertrand, Fabrice</creator><creator>Longden, Thomas A</creator><creator>Ferris, Hannah R</creator><creator>Wellman, George C</creator><creator>Hill-Eubanks, David C</creator><creator>Greenstein, Adam S</creator><creator>Nelson, Mark T</creator><general>American Society for Clinical Investigation</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>IOV</scope><scope>ISR</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2541-9185</orcidid><orcidid>https://orcid.org/0000-0003-2061-1100</orcidid><orcidid>https://orcid.org/0000-0002-7950-7677</orcidid></search><sort><creationdate>20210915</creationdate><title>Differential restoration of functional hyperemia by antihypertensive drug classes in hypertension-related cerebral small vessel disease</title><author>Koide, Masayo ; Harraz, Osama F ; Dabertrand, Fabrice ; Longden, Thomas A ; Ferris, Hannah R ; Wellman, George C ; Hill-Eubanks, David C ; Greenstein, Adam S ; Nelson, Mark T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c619t-1e221a27a2b8bd577651b1c210114d42517fefc6841a2a9474936c58787220c53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Amlodipine - therapeutic use</topic><topic>Angiotensin II Type 1 Receptor Blockers - administration & dosage</topic><topic>Angiotensin II Type 1 Receptor Blockers - therapeutic use</topic><topic>Animals</topic><topic>Antihypertensive Agents - administration & dosage</topic><topic>Antihypertensive Agents - therapeutic use</topic><topic>Antihypertensive drugs</topic><topic>Blood circulation</topic><topic>Cerebral Small Vessel Diseases - drug therapy</topic><topic>Cerebral Small Vessel Diseases - etiology</topic><topic>Cerebral Small Vessel Diseases - physiopathology</topic><topic>Cerebrovascular Circulation - drug effects</topic><topic>Cerebrovascular Circulation - physiology</topic><topic>Cerebrovascular disease</topic><topic>Complications and side effects</topic><topic>Concise Communication</topic><topic>Dementia, Vascular - drug therapy</topic><topic>Dementia, Vascular - etiology</topic><topic>Dementia, Vascular - physiopathology</topic><topic>Disease Models, Animal</topic><topic>Drug therapy</topic><topic>Drug Therapy, Combination</topic><topic>Eplerenone - administration & dosage</topic><topic>Eplerenone - therapeutic use</topic><topic>Health aspects</topic><topic>Heart Disease Risk Factors</topic><topic>Humans</topic><topic>Hyperemia - drug therapy</topic><topic>Hyperemia - physiopathology</topic><topic>Hypertension</topic><topic>Hypertension - complications</topic><topic>Hypertension - drug therapy</topic><topic>Losartan - administration & dosage</topic><topic>Losartan - therapeutic use</topic><topic>Male</topic><topic>Mice</topic><topic>Microvessels - drug effects</topic><topic>Microvessels - physiopathology</topic><topic>Pharmacology, Experimental</topic><topic>Potassium Channels, Inwardly Rectifying - drug effects</topic><topic>Potassium Channels, Inwardly Rectifying - physiology</topic><topic>Renin-Angiotensin System - drug effects</topic><topic>Renin-Angiotensin System - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Koide, Masayo</creatorcontrib><creatorcontrib>Harraz, Osama F</creatorcontrib><creatorcontrib>Dabertrand, Fabrice</creatorcontrib><creatorcontrib>Longden, Thomas A</creatorcontrib><creatorcontrib>Ferris, Hannah R</creatorcontrib><creatorcontrib>Wellman, George C</creatorcontrib><creatorcontrib>Hill-Eubanks, David C</creatorcontrib><creatorcontrib>Greenstein, Adam S</creatorcontrib><creatorcontrib>Nelson, Mark T</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of clinical investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Koide, Masayo</au><au>Harraz, Osama F</au><au>Dabertrand, Fabrice</au><au>Longden, Thomas A</au><au>Ferris, Hannah R</au><au>Wellman, George C</au><au>Hill-Eubanks, David C</au><au>Greenstein, Adam S</au><au>Nelson, Mark T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Differential restoration of functional hyperemia by antihypertensive drug classes in hypertension-related cerebral small vessel disease</atitle><jtitle>The Journal of clinical investigation</jtitle><addtitle>J Clin Invest</addtitle><date>2021-09-15</date><risdate>2021</risdate><volume>131</volume><issue>18</issue><issn>1558-8238</issn><issn>0021-9738</issn><eissn>1558-8238</eissn><abstract>Dementia resulting from small vessel diseases (SVDs) of the brain is an emerging epidemic for which there is no treatment. Hypertension is the major risk factor for SVDs, but how hypertension damages the brain microcirculation is unclear. Here, we show that chronic hypertension in a mouse model progressively disrupts on-demand delivery of blood to metabolically active areas of the brain (functional hyperemia) through diminished activity of the capillary endothelial cell inward-rectifier potassium channel, Kir2.1. Despite similar efficacy in reducing blood pressure, amlodipine, a voltage-dependent calcium-channel blocker, prevented hypertension-related damage to functional hyperemia whereas losartan, an angiotensin II type 1 receptor blocker, did not. We attribute this drug class effect to losartan-induced aldosterone breakthrough, a phenomenon triggered by pharmacological interruption of the renin-angiotensin pathway leading to elevated plasma aldosterone levels. This hypothesis is supported by the finding that combining losartan with the aldosterone receptor antagonist eplerenone prevented the hypertension-related decline in functional hyperemia. Collectively, these data suggest Kir2.1 as a possible therapeutic target in vascular dementia and indicate that concurrent mineralocorticoid aldosterone receptor blockade may aid in protecting against late-life cognitive decline in hypertensive patients treated with angiotensin II type 1 receptor blockers.</abstract><cop>United States</cop><pub>American Society for Clinical Investigation</pub><pmid>34351870</pmid><doi>10.1172/JCI149029</doi><orcidid>https://orcid.org/0000-0003-2541-9185</orcidid><orcidid>https://orcid.org/0000-0003-2061-1100</orcidid><orcidid>https://orcid.org/0000-0002-7950-7677</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1558-8238 |
| ispartof | The Journal of clinical investigation, 2021-09, Vol.131 (18) |
| issn | 1558-8238 0021-9738 1558-8238 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8439604 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Amlodipine - therapeutic use Angiotensin II Type 1 Receptor Blockers - administration & dosage Angiotensin II Type 1 Receptor Blockers - therapeutic use Animals Antihypertensive Agents - administration & dosage Antihypertensive Agents - therapeutic use Antihypertensive drugs Blood circulation Cerebral Small Vessel Diseases - drug therapy Cerebral Small Vessel Diseases - etiology Cerebral Small Vessel Diseases - physiopathology Cerebrovascular Circulation - drug effects Cerebrovascular Circulation - physiology Cerebrovascular disease Complications and side effects Concise Communication Dementia, Vascular - drug therapy Dementia, Vascular - etiology Dementia, Vascular - physiopathology Disease Models, Animal Drug therapy Drug Therapy, Combination Eplerenone - administration & dosage Eplerenone - therapeutic use Health aspects Heart Disease Risk Factors Humans Hyperemia - drug therapy Hyperemia - physiopathology Hypertension Hypertension - complications Hypertension - drug therapy Losartan - administration & dosage Losartan - therapeutic use Male Mice Microvessels - drug effects Microvessels - physiopathology Pharmacology, Experimental Potassium Channels, Inwardly Rectifying - drug effects Potassium Channels, Inwardly Rectifying - physiology Renin-Angiotensin System - drug effects Renin-Angiotensin System - physiology |
| title | Differential restoration of functional hyperemia by antihypertensive drug classes in hypertension-related cerebral small vessel disease |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-23T18%3A58%3A56IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Differential%20restoration%20of%20functional%20hyperemia%20by%20antihypertensive%20drug%20classes%20in%20hypertension-related%20cerebral%20small%20vessel%20disease&rft.jtitle=The%20Journal%20of%20clinical%20investigation&rft.au=Koide,%20Masayo&rft.date=2021-09-15&rft.volume=131&rft.issue=18&rft.issn=1558-8238&rft.eissn=1558-8238&rft_id=info:doi/10.1172/JCI149029&rft_dat=%3Cgale_pubme%3EA677401844%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2559436724&rft_id=info:pmid/34351870&rft_galeid=A677401844&rfr_iscdi=true |