Blood pressure-decreasing effect of etamicastat alone and in combination with antihypertensive drugs in the spontaneously hypertensive rat
Hyperactivation of the sympathetic nervous system has an important role in the development and progression of arterial hypertension. This study evaluated the efficacy of etamicastat, a dopamine-β-hydroxylase (DβH) inhibitor, in controlling high blood pressure in the spontaneously hypertensive rat (S...
Gespeichert in:
| Veröffentlicht in: | Hypertension research 2015-01, Vol.38 (1), p.30-38 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 38 |
|---|---|
| container_issue | 1 |
| container_start_page | 30 |
| container_title | Hypertension research |
| container_volume | 38 |
| creator | Igreja, Bruno Pires, Nuno Miguel Bonifácio, Maria João Loureiro, Ana Isabel Fernandes-Lopes, Carlos Wright, Lyndon Christopher Soares-da-Silva, Patrício |
| description | Hyperactivation of the sympathetic nervous system has an important role in the development and progression of arterial hypertension. This study evaluated the efficacy of etamicastat, a dopamine-β-hydroxylase (DβH) inhibitor, in controlling high blood pressure in the spontaneously hypertensive rat (SHR), either alone or in combination with other classes of antihypertensives. SHRs were administered with etamicastat by gavage, and its pharmacodynamic and pharmacokinetic properties were evaluated. Etamicastat induced a time-dependent decrease in noradrenaline-to-dopamine ratios in the heart and kidney, and had no effect on catecholamine levels in the frontal cortex of SHRs. Cardiovascular pharmacodynamic effects following administration of etamicastat alone or in combination with other classes of antihypertensive drugs were assessed by telemetry. Etamicastat was evaluated in combination with captopril, losartan, hydrochlorothiazide, metoprolol, prazosin and/or diltiazem. Etamicastat monotherapy induced a dose-dependent reduction in blood pressure without reflex tachycardia. Combination therapy amplified the antihypertensive effects of all tested drugs. In conclusion, inhibition of peripheral DβH with etamicastat, as a monotherapy or combination therapy, may constitute a valid alternative treatment for high blood pressure. |
| doi_str_mv | 10.1038/hr.2014.143 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2331641913</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2331641913</sourcerecordid><originalsourceid>FETCH-LOGICAL-c378t-cadefe115b7063a46248fc7e059cc3d79fc71d2a23080da2e9a2d18a7171779b3</originalsourceid><addsrcrecordid>eNpVkM1KLDEQhYMoOv6s3EvApfSYSnq6O0uvXH9AcKPrpiaptiMzSZukvcwr-NT2oF6QWhR1-DgFH2OnIOYgVHPZx7kUUM6hVDtsBqpsilJCuctmQkNV6EpVB-wwpVchZLPQsM8O5ELqRoKYsY8_qxAsHyKlNEYqLJlImJx_4dR1ZDIPHaeMa2cwZcwcV8ETR2-589yE9dJ5zC54_s_lfsqz6zcDxUw-uXfiNo4vaYvmnngags_oKYxpteG_uIj5mO11uEp08r2P2PPN36fru-Lh8fb--uqhMKpucmHQUkcAi2UtKoVlJcumMzWJhTZG2VpPB1iJUolGWJSkUVposIZpar1UR-z8q3eI4W2klNvXMEY_vWylUlCVoEFN1MUXZWJIKVLXDtGtMW5aEO3We9vHduu9nbxP9Nl357hck_3P_ohWn61dgVg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2331641913</pqid></control><display><type>article</type><title>Blood pressure-decreasing effect of etamicastat alone and in combination with antihypertensive drugs in the spontaneously hypertensive rat</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Igreja, Bruno ; Pires, Nuno Miguel ; Bonifácio, Maria João ; Loureiro, Ana Isabel ; Fernandes-Lopes, Carlos ; Wright, Lyndon Christopher ; Soares-da-Silva, Patrício</creator><creatorcontrib>Igreja, Bruno ; Pires, Nuno Miguel ; Bonifácio, Maria João ; Loureiro, Ana Isabel ; Fernandes-Lopes, Carlos ; Wright, Lyndon Christopher ; Soares-da-Silva, Patrício</creatorcontrib><description>Hyperactivation of the sympathetic nervous system has an important role in the development and progression of arterial hypertension. This study evaluated the efficacy of etamicastat, a dopamine-β-hydroxylase (DβH) inhibitor, in controlling high blood pressure in the spontaneously hypertensive rat (SHR), either alone or in combination with other classes of antihypertensives. SHRs were administered with etamicastat by gavage, and its pharmacodynamic and pharmacokinetic properties were evaluated. Etamicastat induced a time-dependent decrease in noradrenaline-to-dopamine ratios in the heart and kidney, and had no effect on catecholamine levels in the frontal cortex of SHRs. Cardiovascular pharmacodynamic effects following administration of etamicastat alone or in combination with other classes of antihypertensive drugs were assessed by telemetry. Etamicastat was evaluated in combination with captopril, losartan, hydrochlorothiazide, metoprolol, prazosin and/or diltiazem. Etamicastat monotherapy induced a dose-dependent reduction in blood pressure without reflex tachycardia. Combination therapy amplified the antihypertensive effects of all tested drugs. In conclusion, inhibition of peripheral DβH with etamicastat, as a monotherapy or combination therapy, may constitute a valid alternative treatment for high blood pressure.</description><identifier>ISSN: 0916-9636</identifier><identifier>EISSN: 1348-4214</identifier><identifier>DOI: 10.1038/hr.2014.143</identifier><identifier>PMID: 25298210</identifier><language>eng</language><publisher>England: Nature Publishing Group</publisher><subject>Animals ; Antihypertensive Agents - pharmacokinetics ; Antihypertensive Agents - therapeutic use ; Antihypertensives ; Benzopyrans - pharmacokinetics ; Benzopyrans - therapeutic use ; Blood pressure ; Blood Pressure - drug effects ; Catecholamines - metabolism ; Disease Models, Animal ; Dopamine ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical ; Drug Therapy, Combination ; Hypertension ; Hypertension - blood ; Hypertension - drug therapy ; Imidazoles - pharmacokinetics ; Imidazoles - therapeutic use ; Kidney - drug effects ; Male ; Rats, Inbred SHR</subject><ispartof>Hypertension research, 2015-01, Vol.38 (1), p.30-38</ispartof><rights>Copyright Nature Publishing Group Jan 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c378t-cadefe115b7063a46248fc7e059cc3d79fc71d2a23080da2e9a2d18a7171779b3</citedby><cites>FETCH-LOGICAL-c378t-cadefe115b7063a46248fc7e059cc3d79fc71d2a23080da2e9a2d18a7171779b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25298210$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Igreja, Bruno</creatorcontrib><creatorcontrib>Pires, Nuno Miguel</creatorcontrib><creatorcontrib>Bonifácio, Maria João</creatorcontrib><creatorcontrib>Loureiro, Ana Isabel</creatorcontrib><creatorcontrib>Fernandes-Lopes, Carlos</creatorcontrib><creatorcontrib>Wright, Lyndon Christopher</creatorcontrib><creatorcontrib>Soares-da-Silva, Patrício</creatorcontrib><title>Blood pressure-decreasing effect of etamicastat alone and in combination with antihypertensive drugs in the spontaneously hypertensive rat</title><title>Hypertension research</title><addtitle>Hypertens Res</addtitle><description>Hyperactivation of the sympathetic nervous system has an important role in the development and progression of arterial hypertension. This study evaluated the efficacy of etamicastat, a dopamine-β-hydroxylase (DβH) inhibitor, in controlling high blood pressure in the spontaneously hypertensive rat (SHR), either alone or in combination with other classes of antihypertensives. SHRs were administered with etamicastat by gavage, and its pharmacodynamic and pharmacokinetic properties were evaluated. Etamicastat induced a time-dependent decrease in noradrenaline-to-dopamine ratios in the heart and kidney, and had no effect on catecholamine levels in the frontal cortex of SHRs. Cardiovascular pharmacodynamic effects following administration of etamicastat alone or in combination with other classes of antihypertensive drugs were assessed by telemetry. Etamicastat was evaluated in combination with captopril, losartan, hydrochlorothiazide, metoprolol, prazosin and/or diltiazem. Etamicastat monotherapy induced a dose-dependent reduction in blood pressure without reflex tachycardia. Combination therapy amplified the antihypertensive effects of all tested drugs. In conclusion, inhibition of peripheral DβH with etamicastat, as a monotherapy or combination therapy, may constitute a valid alternative treatment for high blood pressure.</description><subject>Animals</subject><subject>Antihypertensive Agents - pharmacokinetics</subject><subject>Antihypertensive Agents - therapeutic use</subject><subject>Antihypertensives</subject><subject>Benzopyrans - pharmacokinetics</subject><subject>Benzopyrans - therapeutic use</subject><subject>Blood pressure</subject><subject>Blood Pressure - drug effects</subject><subject>Catecholamines - metabolism</subject><subject>Disease Models, Animal</subject><subject>Dopamine</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Evaluation, Preclinical</subject><subject>Drug Therapy, Combination</subject><subject>Hypertension</subject><subject>Hypertension - blood</subject><subject>Hypertension - drug therapy</subject><subject>Imidazoles - pharmacokinetics</subject><subject>Imidazoles - therapeutic use</subject><subject>Kidney - drug effects</subject><subject>Male</subject><subject>Rats, Inbred SHR</subject><issn>0916-9636</issn><issn>1348-4214</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNpVkM1KLDEQhYMoOv6s3EvApfSYSnq6O0uvXH9AcKPrpiaptiMzSZukvcwr-NT2oF6QWhR1-DgFH2OnIOYgVHPZx7kUUM6hVDtsBqpsilJCuctmQkNV6EpVB-wwpVchZLPQsM8O5ELqRoKYsY8_qxAsHyKlNEYqLJlImJx_4dR1ZDIPHaeMa2cwZcwcV8ETR2-589yE9dJ5zC54_s_lfsqz6zcDxUw-uXfiNo4vaYvmnngags_oKYxpteG_uIj5mO11uEp08r2P2PPN36fru-Lh8fb--uqhMKpucmHQUkcAi2UtKoVlJcumMzWJhTZG2VpPB1iJUolGWJSkUVposIZpar1UR-z8q3eI4W2klNvXMEY_vWylUlCVoEFN1MUXZWJIKVLXDtGtMW5aEO3We9vHduu9nbxP9Nl357hck_3P_ohWn61dgVg</recordid><startdate>20150101</startdate><enddate>20150101</enddate><creator>Igreja, Bruno</creator><creator>Pires, Nuno Miguel</creator><creator>Bonifácio, Maria João</creator><creator>Loureiro, Ana Isabel</creator><creator>Fernandes-Lopes, Carlos</creator><creator>Wright, Lyndon Christopher</creator><creator>Soares-da-Silva, Patrício</creator><general>Nature Publishing Group</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20150101</creationdate><title>Blood pressure-decreasing effect of etamicastat alone and in combination with antihypertensive drugs in the spontaneously hypertensive rat</title><author>Igreja, Bruno ; Pires, Nuno Miguel ; Bonifácio, Maria João ; Loureiro, Ana Isabel ; Fernandes-Lopes, Carlos ; Wright, Lyndon Christopher ; Soares-da-Silva, Patrício</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c378t-cadefe115b7063a46248fc7e059cc3d79fc71d2a23080da2e9a2d18a7171779b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Antihypertensive Agents - pharmacokinetics</topic><topic>Antihypertensive Agents - therapeutic use</topic><topic>Antihypertensives</topic><topic>Benzopyrans - pharmacokinetics</topic><topic>Benzopyrans - therapeutic use</topic><topic>Blood pressure</topic><topic>Blood Pressure - drug effects</topic><topic>Catecholamines - metabolism</topic><topic>Disease Models, Animal</topic><topic>Dopamine</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Evaluation, Preclinical</topic><topic>Drug Therapy, Combination</topic><topic>Hypertension</topic><topic>Hypertension - blood</topic><topic>Hypertension - drug therapy</topic><topic>Imidazoles - pharmacokinetics</topic><topic>Imidazoles - therapeutic use</topic><topic>Kidney - drug effects</topic><topic>Male</topic><topic>Rats, Inbred SHR</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Igreja, Bruno</creatorcontrib><creatorcontrib>Pires, Nuno Miguel</creatorcontrib><creatorcontrib>Bonifácio, Maria João</creatorcontrib><creatorcontrib>Loureiro, Ana Isabel</creatorcontrib><creatorcontrib>Fernandes-Lopes, Carlos</creatorcontrib><creatorcontrib>Wright, Lyndon Christopher</creatorcontrib><creatorcontrib>Soares-da-Silva, Patrício</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical 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><jtitle>Hypertension research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Igreja, Bruno</au><au>Pires, Nuno Miguel</au><au>Bonifácio, Maria João</au><au>Loureiro, Ana Isabel</au><au>Fernandes-Lopes, Carlos</au><au>Wright, Lyndon Christopher</au><au>Soares-da-Silva, Patrício</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Blood pressure-decreasing effect of etamicastat alone and in combination with antihypertensive drugs in the spontaneously hypertensive rat</atitle><jtitle>Hypertension research</jtitle><addtitle>Hypertens Res</addtitle><date>2015-01-01</date><risdate>2015</risdate><volume>38</volume><issue>1</issue><spage>30</spage><epage>38</epage><pages>30-38</pages><issn>0916-9636</issn><eissn>1348-4214</eissn><abstract>Hyperactivation of the sympathetic nervous system has an important role in the development and progression of arterial hypertension. This study evaluated the efficacy of etamicastat, a dopamine-β-hydroxylase (DβH) inhibitor, in controlling high blood pressure in the spontaneously hypertensive rat (SHR), either alone or in combination with other classes of antihypertensives. SHRs were administered with etamicastat by gavage, and its pharmacodynamic and pharmacokinetic properties were evaluated. Etamicastat induced a time-dependent decrease in noradrenaline-to-dopamine ratios in the heart and kidney, and had no effect on catecholamine levels in the frontal cortex of SHRs. Cardiovascular pharmacodynamic effects following administration of etamicastat alone or in combination with other classes of antihypertensive drugs were assessed by telemetry. Etamicastat was evaluated in combination with captopril, losartan, hydrochlorothiazide, metoprolol, prazosin and/or diltiazem. Etamicastat monotherapy induced a dose-dependent reduction in blood pressure without reflex tachycardia. Combination therapy amplified the antihypertensive effects of all tested drugs. In conclusion, inhibition of peripheral DβH with etamicastat, as a monotherapy or combination therapy, may constitute a valid alternative treatment for high blood pressure.</abstract><cop>England</cop><pub>Nature Publishing Group</pub><pmid>25298210</pmid><doi>10.1038/hr.2014.143</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0916-9636 |
| ispartof | Hypertension research, 2015-01, Vol.38 (1), p.30-38 |
| issn | 0916-9636 1348-4214 |
| language | eng |
| recordid | cdi_proquest_journals_2331641913 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Animals Antihypertensive Agents - pharmacokinetics Antihypertensive Agents - therapeutic use Antihypertensives Benzopyrans - pharmacokinetics Benzopyrans - therapeutic use Blood pressure Blood Pressure - drug effects Catecholamines - metabolism Disease Models, Animal Dopamine Dose-Response Relationship, Drug Drug Evaluation, Preclinical Drug Therapy, Combination Hypertension Hypertension - blood Hypertension - drug therapy Imidazoles - pharmacokinetics Imidazoles - therapeutic use Kidney - drug effects Male Rats, Inbred SHR |
| title | Blood pressure-decreasing effect of etamicastat alone and in combination with antihypertensive drugs in the spontaneously hypertensive rat |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-12T15%3A54%3A35IST&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=Blood%20pressure-decreasing%20effect%20of%20etamicastat%20alone%20and%20in%20combination%20with%20antihypertensive%20drugs%20in%20the%20spontaneously%20hypertensive%20rat&rft.jtitle=Hypertension%20research&rft.au=Igreja,%20Bruno&rft.date=2015-01-01&rft.volume=38&rft.issue=1&rft.spage=30&rft.epage=38&rft.pages=30-38&rft.issn=0916-9636&rft.eissn=1348-4214&rft_id=info:doi/10.1038/hr.2014.143&rft_dat=%3Cproquest_cross%3E2331641913%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=2331641913&rft_id=info:pmid/25298210&rfr_iscdi=true |