Endogenous Endothelin in Human Coronary Vascular Function: Differential Contribution of Endothelin Receptor Types A and B
Endothelin 1 mediates coronary vasoconstriction and endothelial dysfunction via endothelin receptor type A (ETA) activation. However, the effects of selective endothelin receptor type B (ETB) and combined ETA+B receptor blockade on coronary vasomotion are unknown. We measured coronary vascular tone...
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| Veröffentlicht in: | Hypertension (Dallas, Tex. 1979) Tex. 1979), 2007-05, Vol.49 (5), p.1134-1141 |
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| creator | Halcox, Julian P.J Nour, Khaled R.A Zalos, Gloria Quyyumi, Arshed A |
| description | Endothelin 1 mediates coronary vasoconstriction and endothelial dysfunction via endothelin receptor type A (ETA) activation. However, the effects of selective endothelin receptor type B (ETB) and combined ETA+B receptor blockade on coronary vasomotion are unknown. We measured coronary vascular tone and endothelium-dependent and -independent vasomotor function before and after selective infusion of BQ-788 (an ETB receptor antagonist) or combined infusion of BQ-788+BQ-123 (an ETA antagonist) into unobstructed coronary arteries of 39 patients with coronary atherosclerosis or risk factors undergoing cardiac catheterization. BQ-788 did not affect epicardial diameter but constricted the microcirculation (P |
| doi_str_mv | 10.1161/HYPERTENSIONAHA.106.083303 |
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However, the effects of selective endothelin receptor type B (ETB) and combined ETA+B receptor blockade on coronary vasomotion are unknown. We measured coronary vascular tone and endothelium-dependent and -independent vasomotor function before and after selective infusion of BQ-788 (an ETB receptor antagonist) or combined infusion of BQ-788+BQ-123 (an ETA antagonist) into unobstructed coronary arteries of 39 patients with coronary atherosclerosis or risk factors undergoing cardiac catheterization. BQ-788 did not affect epicardial diameter but constricted the microcirculation (P<0.0001), increased coronary sinus endothelin, and reduced nitrogen oxide levels. In contrast, BQ-123+BQ-788 dilated epicardial (P<0.0001) and resistance (P=0.022) arteries. Responses to acetylcholine and sodium nitroprusside were unaffected by BQ-788 alone. Epicardial endothelial dysfunction improved after BQ-123+BQ-788 (P=0.007). Coronary microvascular responses to acetylcholine and sodium nitroprusside were unaffected by BQ-123+BQ-788. We conclude that selective ETB receptor antagonism causes coronary microvascular constriction, without affecting epicardial tone or endothelial function, via reduced endothelin clearance and NO availability. Combined ETA+B blockade dilates coronary conduit and resistance vessels and improves endothelial dysfunction of the epicardial coronary arteries. Thus, endogenous endothelin, predominantly via ETA receptor stimulation, contributes to basal constrictor tone and endothelial dysfunction, whereas ETB activation mediates vasodilation in human coronaries. Our data suggest that selective ETA blockade may have greater therapeutic potential than nonselective agents, particularly for treatment of endothelial dysfunction in atherosclerosis.</description><identifier>ISSN: 0194-911X</identifier><identifier>EISSN: 1524-4563</identifier><identifier>DOI: 10.1161/HYPERTENSIONAHA.106.083303</identifier><identifier>PMID: 17353514</identifier><identifier>CODEN: HPRTDN</identifier><language>eng</language><publisher>Philadelphia, PA: American Heart Association, Inc</publisher><subject>Arterial hypertension. Arterial hypotension ; Biological and medical sciences ; Blood and lymphatic vessels ; Blood vessels and receptors ; Cardiology. Vascular system ; Clinical manifestations. Epidemiology. Investigative techniques. Etiology ; Coronary Artery Disease - metabolism ; Coronary Artery Disease - physiopathology ; Coronary Circulation - drug effects ; Coronary Vessels - drug effects ; Coronary Vessels - physiopathology ; Drug Combinations ; Endothelin A Receptor Antagonists ; Endothelin B Receptor Antagonists ; Endothelin-1 - blood ; Endothelin-1 - metabolism ; Endothelium, Vascular - physiopathology ; Fundamental and applied biological sciences. Psychology ; Humans ; Medical sciences ; Microcirculation - drug effects ; Nitrogen Oxides - blood ; Oligopeptides - pharmacology ; Peptides, Cyclic - pharmacology ; Pericardium ; Piperidines - pharmacology ; Receptor, Endothelin A - metabolism ; Receptor, Endothelin B - metabolism ; Vasoconstriction ; Vasodilation ; Vasomotor System - drug effects ; Vertebrates: cardiovascular system</subject><ispartof>Hypertension (Dallas, Tex. 1979), 2007-05, Vol.49 (5), p.1134-1141</ispartof><rights>2007 American Heart Association, Inc.</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3873-9d3419883b7bec90fdc32642827914c6652d6781092170cdc78745c2a3f87ab53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,3688,27929,27930</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18700315$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17353514$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Halcox, Julian P.J</creatorcontrib><creatorcontrib>Nour, Khaled R.A</creatorcontrib><creatorcontrib>Zalos, Gloria</creatorcontrib><creatorcontrib>Quyyumi, Arshed A</creatorcontrib><title>Endogenous Endothelin in Human Coronary Vascular Function: Differential Contribution of Endothelin Receptor Types A and B</title><title>Hypertension (Dallas, Tex. 1979)</title><addtitle>Hypertension</addtitle><description>Endothelin 1 mediates coronary vasoconstriction and endothelial dysfunction via endothelin receptor type A (ETA) activation. However, the effects of selective endothelin receptor type B (ETB) and combined ETA+B receptor blockade on coronary vasomotion are unknown. We measured coronary vascular tone and endothelium-dependent and -independent vasomotor function before and after selective infusion of BQ-788 (an ETB receptor antagonist) or combined infusion of BQ-788+BQ-123 (an ETA antagonist) into unobstructed coronary arteries of 39 patients with coronary atherosclerosis or risk factors undergoing cardiac catheterization. BQ-788 did not affect epicardial diameter but constricted the microcirculation (P<0.0001), increased coronary sinus endothelin, and reduced nitrogen oxide levels. In contrast, BQ-123+BQ-788 dilated epicardial (P<0.0001) and resistance (P=0.022) arteries. Responses to acetylcholine and sodium nitroprusside were unaffected by BQ-788 alone. Epicardial endothelial dysfunction improved after BQ-123+BQ-788 (P=0.007). Coronary microvascular responses to acetylcholine and sodium nitroprusside were unaffected by BQ-123+BQ-788. We conclude that selective ETB receptor antagonism causes coronary microvascular constriction, without affecting epicardial tone or endothelial function, via reduced endothelin clearance and NO availability. Combined ETA+B blockade dilates coronary conduit and resistance vessels and improves endothelial dysfunction of the epicardial coronary arteries. Thus, endogenous endothelin, predominantly via ETA receptor stimulation, contributes to basal constrictor tone and endothelial dysfunction, whereas ETB activation mediates vasodilation in human coronaries. Our data suggest that selective ETA blockade may have greater therapeutic potential than nonselective agents, particularly for treatment of endothelial dysfunction in atherosclerosis.</description><subject>Arterial hypertension. Arterial hypotension</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Blood vessels and receptors</subject><subject>Cardiology. Vascular system</subject><subject>Clinical manifestations. Epidemiology. Investigative techniques. Etiology</subject><subject>Coronary Artery Disease - metabolism</subject><subject>Coronary Artery Disease - physiopathology</subject><subject>Coronary Circulation - drug effects</subject><subject>Coronary Vessels - drug effects</subject><subject>Coronary Vessels - physiopathology</subject><subject>Drug Combinations</subject><subject>Endothelin A Receptor Antagonists</subject><subject>Endothelin B Receptor Antagonists</subject><subject>Endothelin-1 - blood</subject><subject>Endothelin-1 - metabolism</subject><subject>Endothelium, Vascular - physiopathology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Microcirculation - drug effects</subject><subject>Nitrogen Oxides - blood</subject><subject>Oligopeptides - pharmacology</subject><subject>Peptides, Cyclic - pharmacology</subject><subject>Pericardium</subject><subject>Piperidines - pharmacology</subject><subject>Receptor, Endothelin A - metabolism</subject><subject>Receptor, Endothelin B - metabolism</subject><subject>Vasoconstriction</subject><subject>Vasodilation</subject><subject>Vasomotor System - drug effects</subject><subject>Vertebrates: cardiovascular system</subject><issn>0194-911X</issn><issn>1524-4563</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkFFr2zAQgMVYWbNuf6GIwfbmTGfJltyHQZamS6G0o0vL9mRk-dx4U6RUsin597NJoGVPA8EJ3Xenu4-QD8CmADl8Xv76vrhdLa5_XN5cz5azKbB8yhTnjL8iE8hSkYgs56_JhEEhkgLg5zF5G-NvxkAIId-QY5A84xmICdktXO0f0Pk-0vHardG2jg5n2W-0o3MfvNNhR-91NL3VgV70znStd2f0vG0aDOi6VtsBdF1oq35MUd-8bHaLBredD3S122KkM6pdTb--I0eNthHfH-IJubtYrObL5Orm2-V8dpUYriRPipoLKJTilazQFKypDU9zkapUFiBMnmdpnUsFrEhBMlMbqaTITKp5o6SuMn5CPu37boN_7DF25aaNBq3VDoetS8m4Umkxgmd70AQfY8Cm3IZ2M-xeAitH8eU_4of3vNyLH4pPD7_01Qbr59KD6QH4eAAGkdo2QTvTxmdOScY4jFN82XNP3nYY4h_bP2Eo16htt_6fSf4C_GGhzA</recordid><startdate>200705</startdate><enddate>200705</enddate><creator>Halcox, Julian P.J</creator><creator>Nour, Khaled R.A</creator><creator>Zalos, Gloria</creator><creator>Quyyumi, Arshed A</creator><general>American Heart Association, Inc</general><general>Lippincott</general><scope>IQODW</scope><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>200705</creationdate><title>Endogenous Endothelin in Human Coronary Vascular Function: Differential Contribution of Endothelin Receptor Types A and B</title><author>Halcox, Julian P.J ; Nour, Khaled R.A ; Zalos, Gloria ; Quyyumi, Arshed A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3873-9d3419883b7bec90fdc32642827914c6652d6781092170cdc78745c2a3f87ab53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Arterial hypertension. Arterial hypotension</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Blood vessels and receptors</topic><topic>Cardiology. Vascular system</topic><topic>Clinical manifestations. Epidemiology. Investigative techniques. Etiology</topic><topic>Coronary Artery Disease - metabolism</topic><topic>Coronary Artery Disease - physiopathology</topic><topic>Coronary Circulation - drug effects</topic><topic>Coronary Vessels - drug effects</topic><topic>Coronary Vessels - physiopathology</topic><topic>Drug Combinations</topic><topic>Endothelin A Receptor Antagonists</topic><topic>Endothelin B Receptor Antagonists</topic><topic>Endothelin-1 - blood</topic><topic>Endothelin-1 - metabolism</topic><topic>Endothelium, Vascular - physiopathology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Microcirculation - drug effects</topic><topic>Nitrogen Oxides - blood</topic><topic>Oligopeptides - pharmacology</topic><topic>Peptides, Cyclic - pharmacology</topic><topic>Pericardium</topic><topic>Piperidines - pharmacology</topic><topic>Receptor, Endothelin A - metabolism</topic><topic>Receptor, Endothelin B - metabolism</topic><topic>Vasoconstriction</topic><topic>Vasodilation</topic><topic>Vasomotor System - drug effects</topic><topic>Vertebrates: cardiovascular system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Halcox, Julian P.J</creatorcontrib><creatorcontrib>Nour, Khaled R.A</creatorcontrib><creatorcontrib>Zalos, Gloria</creatorcontrib><creatorcontrib>Quyyumi, Arshed A</creatorcontrib><collection>Pascal-Francis</collection><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>Hypertension (Dallas, Tex. 1979)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Halcox, Julian P.J</au><au>Nour, Khaled R.A</au><au>Zalos, Gloria</au><au>Quyyumi, Arshed A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Endogenous Endothelin in Human Coronary Vascular Function: Differential Contribution of Endothelin Receptor Types A and B</atitle><jtitle>Hypertension (Dallas, Tex. 1979)</jtitle><addtitle>Hypertension</addtitle><date>2007-05</date><risdate>2007</risdate><volume>49</volume><issue>5</issue><spage>1134</spage><epage>1141</epage><pages>1134-1141</pages><issn>0194-911X</issn><eissn>1524-4563</eissn><coden>HPRTDN</coden><abstract>Endothelin 1 mediates coronary vasoconstriction and endothelial dysfunction via endothelin receptor type A (ETA) activation. However, the effects of selective endothelin receptor type B (ETB) and combined ETA+B receptor blockade on coronary vasomotion are unknown. We measured coronary vascular tone and endothelium-dependent and -independent vasomotor function before and after selective infusion of BQ-788 (an ETB receptor antagonist) or combined infusion of BQ-788+BQ-123 (an ETA antagonist) into unobstructed coronary arteries of 39 patients with coronary atherosclerosis or risk factors undergoing cardiac catheterization. BQ-788 did not affect epicardial diameter but constricted the microcirculation (P<0.0001), increased coronary sinus endothelin, and reduced nitrogen oxide levels. In contrast, BQ-123+BQ-788 dilated epicardial (P<0.0001) and resistance (P=0.022) arteries. Responses to acetylcholine and sodium nitroprusside were unaffected by BQ-788 alone. Epicardial endothelial dysfunction improved after BQ-123+BQ-788 (P=0.007). Coronary microvascular responses to acetylcholine and sodium nitroprusside were unaffected by BQ-123+BQ-788. We conclude that selective ETB receptor antagonism causes coronary microvascular constriction, without affecting epicardial tone or endothelial function, via reduced endothelin clearance and NO availability. Combined ETA+B blockade dilates coronary conduit and resistance vessels and improves endothelial dysfunction of the epicardial coronary arteries. Thus, endogenous endothelin, predominantly via ETA receptor stimulation, contributes to basal constrictor tone and endothelial dysfunction, whereas ETB activation mediates vasodilation in human coronaries. Our data suggest that selective ETA blockade may have greater therapeutic potential than nonselective agents, particularly for treatment of endothelial dysfunction in atherosclerosis.</abstract><cop>Philadelphia, PA</cop><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>17353514</pmid><doi>10.1161/HYPERTENSIONAHA.106.083303</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0194-911X |
| ispartof | Hypertension (Dallas, Tex. 1979), 2007-05, Vol.49 (5), p.1134-1141 |
| issn | 0194-911X 1524-4563 |
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| source | MEDLINE; American Heart Association Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Complete |
| subjects | Arterial hypertension. Arterial hypotension Biological and medical sciences Blood and lymphatic vessels Blood vessels and receptors Cardiology. Vascular system Clinical manifestations. Epidemiology. Investigative techniques. Etiology Coronary Artery Disease - metabolism Coronary Artery Disease - physiopathology Coronary Circulation - drug effects Coronary Vessels - drug effects Coronary Vessels - physiopathology Drug Combinations Endothelin A Receptor Antagonists Endothelin B Receptor Antagonists Endothelin-1 - blood Endothelin-1 - metabolism Endothelium, Vascular - physiopathology Fundamental and applied biological sciences. Psychology Humans Medical sciences Microcirculation - drug effects Nitrogen Oxides - blood Oligopeptides - pharmacology Peptides, Cyclic - pharmacology Pericardium Piperidines - pharmacology Receptor, Endothelin A - metabolism Receptor, Endothelin B - metabolism Vasoconstriction Vasodilation Vasomotor System - drug effects Vertebrates: cardiovascular system |
| title | Endogenous Endothelin in Human Coronary Vascular Function: Differential Contribution of Endothelin Receptor Types A and B |
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