Endothelin-A receptor antagonism reduces blood pressure and increases renal blood flow in hypertensive patients with chronic renal failure: A comparison of selective and combined endothelin receptor blockade
Endothelin (ET) is implicated in the pathophysiology of chronic renal failure (CRF). We therefore studied the systemic and renal hemodynamic effects of ET receptor antagonists in CRF and examined differences between selective ETA, selective ETB, and combined ETA/B receptor blockade. We conducted a r...
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| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 2004-03, Vol.109 (9), p.1186-1193 |
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| creator | GODDARD, Jane JOHNSTON, Neil R HAND, Malcolm F CUMMING, Allan D RABELINK, Ton J RANKIN, Andrew J WEBB, David J |
| description | Endothelin (ET) is implicated in the pathophysiology of chronic renal failure (CRF). We therefore studied the systemic and renal hemodynamic effects of ET receptor antagonists in CRF and examined differences between selective ETA, selective ETB, and combined ETA/B receptor blockade.
We conducted a randomized, placebo-controlled, double-blind, 4-way crossover study comparing selective ET receptor antagonists BQ-123 (ETA) and BQ-788 (ETB), given alone and in combination, in acute studies in 8 hypertensive CRF patients and 8 matched healthy controls. BQ-123, alone and in combination with BQ-788, reduced blood pressure in CRF, particularly with BQ-123 alone (mean arterial pressure: controls -4+/-2%, CRF -13+/-2%, P |
| doi_str_mv | 10.1161/01.CIR.0000118499.69469.51 |
| format | Article |
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We conducted a randomized, placebo-controlled, double-blind, 4-way crossover study comparing selective ET receptor antagonists BQ-123 (ETA) and BQ-788 (ETB), given alone and in combination, in acute studies in 8 hypertensive CRF patients and 8 matched healthy controls. BQ-123, alone and in combination with BQ-788, reduced blood pressure in CRF, particularly with BQ-123 alone (mean arterial pressure: controls -4+/-2%, CRF -13+/-2%, P<0.01 versus placebo). In CRF, in the face of this fall in blood pressure, BQ-123 substantially increased renal blood flow (38.8+/-23.9%, P<0.01 versus placebo) and reduced renal vascular resistance (-44.5+/-11.3%, P<0.01 versus placebo) when given alone but not when combined with BQ-788. These changes were accompanied by a reduction in effective filtration fraction. BQ-123, alone or in combination with BQ-788, had minimal effects on the renal circulation in healthy controls, and BQ-788 alone produced both systemic and renal vasoconstriction in CRF and healthy controls.
ETA receptor antagonism was highly effective in lowering blood pressure in CRF patients currently treated for hypertension. In addition, there were effects consistent with a renoprotective action. However, because the ETB receptor appears to play a key role in the maintenance of tonic renal vasodilation, combined ETA/B receptor antagonism, although it lowered blood pressure, did not confer these renal benefits.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/01.CIR.0000118499.69469.51</identifier><identifier>PMID: 14981006</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Antihypertensive Agents - blood ; Antihypertensive Agents - therapeutic use ; Biological and medical sciences ; Blood and lymphatic vessels ; Blood Pressure - drug effects ; Cardiology. Vascular system ; Cross-Over Studies ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Double-Blind Method ; Endothelin A Receptor Antagonists ; Endothelin B Receptor Antagonists ; Endothelin-1 - blood ; Hemodynamics - drug effects ; Humans ; Hypertension, Renal - drug therapy ; Hypertension, Renal - metabolism ; Hypertension, Renal - physiopathology ; Kidney - physiopathology ; Kidney Failure, Chronic - drug therapy ; Kidney Failure, Chronic - metabolism ; Kidney Failure, Chronic - physiopathology ; Male ; Medical sciences ; Middle Aged ; Oligopeptides - therapeutic use ; Peptides, Cyclic - blood ; Peptides, Cyclic - therapeutic use ; Piperidines - therapeutic use ; Proteinuria - diagnosis ; Renal Circulation - drug effects ; Sodium - urine</subject><ispartof>Circulation (New York, N.Y.), 2004-03, Vol.109 (9), p.1186-1193</ispartof><rights>2004 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Mar 9 2004</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c357t-9e0817712b355dee376da4f9ad3ff3a962bab4695bebfe40a2dc24309b419f1c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3674,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15580703$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14981006$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>GODDARD, Jane</creatorcontrib><creatorcontrib>JOHNSTON, Neil R</creatorcontrib><creatorcontrib>HAND, Malcolm F</creatorcontrib><creatorcontrib>CUMMING, Allan D</creatorcontrib><creatorcontrib>RABELINK, Ton J</creatorcontrib><creatorcontrib>RANKIN, Andrew J</creatorcontrib><creatorcontrib>WEBB, David J</creatorcontrib><title>Endothelin-A receptor antagonism reduces blood pressure and increases renal blood flow in hypertensive patients with chronic renal failure: A comparison of selective and combined endothelin receptor blockade</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>Endothelin (ET) is implicated in the pathophysiology of chronic renal failure (CRF). We therefore studied the systemic and renal hemodynamic effects of ET receptor antagonists in CRF and examined differences between selective ETA, selective ETB, and combined ETA/B receptor blockade.
We conducted a randomized, placebo-controlled, double-blind, 4-way crossover study comparing selective ET receptor antagonists BQ-123 (ETA) and BQ-788 (ETB), given alone and in combination, in acute studies in 8 hypertensive CRF patients and 8 matched healthy controls. BQ-123, alone and in combination with BQ-788, reduced blood pressure in CRF, particularly with BQ-123 alone (mean arterial pressure: controls -4+/-2%, CRF -13+/-2%, P<0.01 versus placebo). In CRF, in the face of this fall in blood pressure, BQ-123 substantially increased renal blood flow (38.8+/-23.9%, P<0.01 versus placebo) and reduced renal vascular resistance (-44.5+/-11.3%, P<0.01 versus placebo) when given alone but not when combined with BQ-788. These changes were accompanied by a reduction in effective filtration fraction. BQ-123, alone or in combination with BQ-788, had minimal effects on the renal circulation in healthy controls, and BQ-788 alone produced both systemic and renal vasoconstriction in CRF and healthy controls.
ETA receptor antagonism was highly effective in lowering blood pressure in CRF patients currently treated for hypertension. In addition, there were effects consistent with a renoprotective action. However, because the ETB receptor appears to play a key role in the maintenance of tonic renal vasodilation, combined ETA/B receptor antagonism, although it lowered blood pressure, did not confer these renal benefits.</description><subject>Antihypertensive Agents - blood</subject><subject>Antihypertensive Agents - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Blood Pressure - drug effects</subject><subject>Cardiology. Vascular system</subject><subject>Cross-Over Studies</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Double-Blind Method</subject><subject>Endothelin A Receptor Antagonists</subject><subject>Endothelin B Receptor Antagonists</subject><subject>Endothelin-1 - blood</subject><subject>Hemodynamics - drug effects</subject><subject>Humans</subject><subject>Hypertension, Renal - drug therapy</subject><subject>Hypertension, Renal - metabolism</subject><subject>Hypertension, Renal - physiopathology</subject><subject>Kidney - physiopathology</subject><subject>Kidney Failure, Chronic - drug therapy</subject><subject>Kidney Failure, Chronic - metabolism</subject><subject>Kidney Failure, Chronic - physiopathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Oligopeptides - therapeutic use</subject><subject>Peptides, Cyclic - blood</subject><subject>Peptides, Cyclic - therapeutic use</subject><subject>Piperidines - therapeutic use</subject><subject>Proteinuria - diagnosis</subject><subject>Renal Circulation - drug effects</subject><subject>Sodium - urine</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkcFu1DAQhiMEokvhFZBVCW5ZMnEcx72tVoVWqoSE4Gw59ph1SexgJ636lLwSXhp1JXyxZub7Z8b-i-ICqi1AC58q2O5vvm2rfAC6RohtK5pWbBm8KDbA6qZsGBUvi00GRMlpXZ8Vb1K6y2FLOXtdnEEjOsjRpvhz5U2YDzg4X-5IRI3THCJRflY_g3dpzDmzaEykH0IwZIqY0hIxE4Y4ryOqlIsRvRpWxA7hIZfI4XHCOKNP7h7JpGaHfk7kwc0Hog8xN9erzCo35JaXZEd0GCcVXQqeBEsSDqjno_w4Ldd659EQfF75tHAerX8pg2-LV1YNCd-t93nx4_PV9_11efv1y81-d1tqyvhcCqw64BzqnjJmEClvjWqsUIZaS5Vo6171-U9Zj73FplK10XVDK9E3ICxoel58fOo7xfB7wTTL0SWNw6A8hiVJDhwYa7oMXvwH3oUl5mcnWUPNGeW8ytDlE6RjSCmilVN0o4qPEip59FxWILPn8uS5_Oe5ZJDF79cJSz-iOUlXkzPwYQVU0mqwUXnt0oljrKvyEvQv4me7Ag</recordid><startdate>20040309</startdate><enddate>20040309</enddate><creator>GODDARD, Jane</creator><creator>JOHNSTON, Neil R</creator><creator>HAND, Malcolm F</creator><creator>CUMMING, Allan D</creator><creator>RABELINK, Ton J</creator><creator>RANKIN, Andrew J</creator><creator>WEBB, David J</creator><general>Lippincott Williams & Wilkins</general><general>American Heart Association, Inc</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>K9.</scope><scope>NAPCQ</scope><scope>U9A</scope><scope>7X8</scope></search><sort><creationdate>20040309</creationdate><title>Endothelin-A receptor antagonism reduces blood pressure and increases renal blood flow in hypertensive patients with chronic renal failure: A comparison of selective and combined endothelin receptor blockade</title><author>GODDARD, Jane ; JOHNSTON, Neil R ; HAND, Malcolm F ; CUMMING, Allan D ; RABELINK, Ton J ; RANKIN, Andrew J ; WEBB, David J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c357t-9e0817712b355dee376da4f9ad3ff3a962bab4695bebfe40a2dc24309b419f1c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Antihypertensive Agents - blood</topic><topic>Antihypertensive Agents - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Blood Pressure - drug effects</topic><topic>Cardiology. Vascular system</topic><topic>Cross-Over Studies</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</topic><topic>Double-Blind Method</topic><topic>Endothelin A Receptor Antagonists</topic><topic>Endothelin B Receptor Antagonists</topic><topic>Endothelin-1 - blood</topic><topic>Hemodynamics - drug effects</topic><topic>Humans</topic><topic>Hypertension, Renal - drug therapy</topic><topic>Hypertension, Renal - metabolism</topic><topic>Hypertension, Renal - physiopathology</topic><topic>Kidney - physiopathology</topic><topic>Kidney Failure, Chronic - drug therapy</topic><topic>Kidney Failure, Chronic - metabolism</topic><topic>Kidney Failure, Chronic - physiopathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Oligopeptides - therapeutic use</topic><topic>Peptides, Cyclic - blood</topic><topic>Peptides, Cyclic - therapeutic use</topic><topic>Piperidines - therapeutic use</topic><topic>Proteinuria - diagnosis</topic><topic>Renal Circulation - drug effects</topic><topic>Sodium - urine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>GODDARD, Jane</creatorcontrib><creatorcontrib>JOHNSTON, Neil R</creatorcontrib><creatorcontrib>HAND, Malcolm F</creatorcontrib><creatorcontrib>CUMMING, Allan D</creatorcontrib><creatorcontrib>RABELINK, Ton J</creatorcontrib><creatorcontrib>RANKIN, Andrew J</creatorcontrib><creatorcontrib>WEBB, David J</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>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>GODDARD, Jane</au><au>JOHNSTON, Neil R</au><au>HAND, Malcolm F</au><au>CUMMING, Allan D</au><au>RABELINK, Ton J</au><au>RANKIN, Andrew J</au><au>WEBB, David J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Endothelin-A receptor antagonism reduces blood pressure and increases renal blood flow in hypertensive patients with chronic renal failure: A comparison of selective and combined endothelin receptor blockade</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2004-03-09</date><risdate>2004</risdate><volume>109</volume><issue>9</issue><spage>1186</spage><epage>1193</epage><pages>1186-1193</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>Endothelin (ET) is implicated in the pathophysiology of chronic renal failure (CRF). We therefore studied the systemic and renal hemodynamic effects of ET receptor antagonists in CRF and examined differences between selective ETA, selective ETB, and combined ETA/B receptor blockade.
We conducted a randomized, placebo-controlled, double-blind, 4-way crossover study comparing selective ET receptor antagonists BQ-123 (ETA) and BQ-788 (ETB), given alone and in combination, in acute studies in 8 hypertensive CRF patients and 8 matched healthy controls. BQ-123, alone and in combination with BQ-788, reduced blood pressure in CRF, particularly with BQ-123 alone (mean arterial pressure: controls -4+/-2%, CRF -13+/-2%, P<0.01 versus placebo). In CRF, in the face of this fall in blood pressure, BQ-123 substantially increased renal blood flow (38.8+/-23.9%, P<0.01 versus placebo) and reduced renal vascular resistance (-44.5+/-11.3%, P<0.01 versus placebo) when given alone but not when combined with BQ-788. These changes were accompanied by a reduction in effective filtration fraction. BQ-123, alone or in combination with BQ-788, had minimal effects on the renal circulation in healthy controls, and BQ-788 alone produced both systemic and renal vasoconstriction in CRF and healthy controls.
ETA receptor antagonism was highly effective in lowering blood pressure in CRF patients currently treated for hypertension. In addition, there were effects consistent with a renoprotective action. However, because the ETB receptor appears to play a key role in the maintenance of tonic renal vasodilation, combined ETA/B receptor antagonism, although it lowered blood pressure, did not confer these renal benefits.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>14981006</pmid><doi>10.1161/01.CIR.0000118499.69469.51</doi><tpages>8</tpages></addata></record> |
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| identifier | ISSN: 0009-7322 |
| ispartof | Circulation (New York, N.Y.), 2004-03, Vol.109 (9), p.1186-1193 |
| issn | 0009-7322 1524-4539 |
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| source | Journals@Ovid Ovid Autoload; MEDLINE; American Heart Association Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Antihypertensive Agents - blood Antihypertensive Agents - therapeutic use Biological and medical sciences Blood and lymphatic vessels Blood Pressure - drug effects Cardiology. Vascular system Cross-Over Studies Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Double-Blind Method Endothelin A Receptor Antagonists Endothelin B Receptor Antagonists Endothelin-1 - blood Hemodynamics - drug effects Humans Hypertension, Renal - drug therapy Hypertension, Renal - metabolism Hypertension, Renal - physiopathology Kidney - physiopathology Kidney Failure, Chronic - drug therapy Kidney Failure, Chronic - metabolism Kidney Failure, Chronic - physiopathology Male Medical sciences Middle Aged Oligopeptides - therapeutic use Peptides, Cyclic - blood Peptides, Cyclic - therapeutic use Piperidines - therapeutic use Proteinuria - diagnosis Renal Circulation - drug effects Sodium - urine |
| title | Endothelin-A receptor antagonism reduces blood pressure and increases renal blood flow in hypertensive patients with chronic renal failure: A comparison of selective and combined endothelin receptor blockade |
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