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Article: Use of A-192621 and IRL-2500 to unmask the mesenteric and renal vasodilator role of endothelin ETB receptors

TitleUse of A-192621 and IRL-2500 to unmask the mesenteric and renal vasodilator role of endothelin ETB receptors
Authors
KeywordsBlood pressure
Cardiac output
Conductance
Endothelin-1
Mesenteric blood flow
Renal blood flow
Issue Date2002
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.cardiovascularpharm.com/
Citation
Journal Of Cardiovascular Pharmacology, 2002, v. 39 n. 4, p. 533-543 How to Cite?
AbstractEndothelin-1 (ET-1) is known to cause a transient (<1 min) depressor followed by a sustained (>1 h) pressor response. The former through the activation of ETB receptors, and the latter through the activation of ETA and ETB receptors. This study examines if ETB receptors mediate sustained mesenteric and renal dilation in anesthetized rats. Intravenous bolus ET-1 (0.8, 1.4, and 2 nmol/kg) and IRL-1620 (ETB agonist, 2, 5, and 10 nmol/kg) caused transient decrease followed by sustained increases in mean arterial pressure (MAP) that were accompanied by increases in total peripheral resistance (TPR), reductions in cardiac output (CO), and mesenteric and renal vasoconstriction. Pretreatment with FR-139317 (ETA antagonist, 1 mg/kg) attenuated the pressor and constrictor effects of ET-1 but did not alter responses to IRL-1620. IRL-2500 (ETB antagonist, 5 mg/kg) slightly inhibited the renal constrictor effect of IRL-1620, whereas A-192621 (ETB antagonist, 5 mg/kg) abolished all hemodynamic responses to IRL-1620. Both IRL-2500 and A-192621 markedly enhanced MAP, TPR, and mesenteric, and the renal constrictor effects of ET-1. Therefore, A-192621 was more effective than IRL-2500 in blocking IRL-1620-induced vasoconstriction, but both augmented constrictor responses to ET-1. The potentiation of ET-1-induced vasoconstriction by ETB receptor antagonists revealed a sustained vasodilator role of ETB receptors.
Persistent Identifierhttp://hdl.handle.net/10722/80229
ISSN
2015 Impact Factor: 2.462
2015 SCImago Journal Rankings: 0.962
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLeung, SWSen_HK
dc.contributor.authorLim, SLen_HK
dc.contributor.authorPang, CCYen_HK
dc.contributor.authorMan, RYKen_HK
dc.date.accessioned2010-09-06T08:03:58Z-
dc.date.available2010-09-06T08:03:58Z-
dc.date.issued2002en_HK
dc.identifier.citationJournal Of Cardiovascular Pharmacology, 2002, v. 39 n. 4, p. 533-543en_HK
dc.identifier.issn0160-2446en_HK
dc.identifier.urihttp://hdl.handle.net/10722/80229-
dc.description.abstractEndothelin-1 (ET-1) is known to cause a transient (<1 min) depressor followed by a sustained (>1 h) pressor response. The former through the activation of ETB receptors, and the latter through the activation of ETA and ETB receptors. This study examines if ETB receptors mediate sustained mesenteric and renal dilation in anesthetized rats. Intravenous bolus ET-1 (0.8, 1.4, and 2 nmol/kg) and IRL-1620 (ETB agonist, 2, 5, and 10 nmol/kg) caused transient decrease followed by sustained increases in mean arterial pressure (MAP) that were accompanied by increases in total peripheral resistance (TPR), reductions in cardiac output (CO), and mesenteric and renal vasoconstriction. Pretreatment with FR-139317 (ETA antagonist, 1 mg/kg) attenuated the pressor and constrictor effects of ET-1 but did not alter responses to IRL-1620. IRL-2500 (ETB antagonist, 5 mg/kg) slightly inhibited the renal constrictor effect of IRL-1620, whereas A-192621 (ETB antagonist, 5 mg/kg) abolished all hemodynamic responses to IRL-1620. Both IRL-2500 and A-192621 markedly enhanced MAP, TPR, and mesenteric, and the renal constrictor effects of ET-1. Therefore, A-192621 was more effective than IRL-2500 in blocking IRL-1620-induced vasoconstriction, but both augmented constrictor responses to ET-1. The potentiation of ET-1-induced vasoconstriction by ETB receptor antagonists revealed a sustained vasodilator role of ETB receptors.en_HK
dc.languageengen_HK
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.cardiovascularpharm.com/en_HK
dc.relation.ispartofJournal of Cardiovascular Pharmacologyen_HK
dc.rightsJournal of Cardiovascular Pharmacology. Copyright © Lippincott Williams & Wilkins.en_HK
dc.subjectBlood pressureen_HK
dc.subjectCardiac outputen_HK
dc.subjectConductanceen_HK
dc.subjectEndothelin-1en_HK
dc.subjectMesenteric blood flowen_HK
dc.subjectRenal blood flowen_HK
dc.titleUse of A-192621 and IRL-2500 to unmask the mesenteric and renal vasodilator role of endothelin ETB receptorsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0160-2446&volume=39&spage=533&epage=543&date=2001&atitle=Use+of+A-192621+and+IRL-2500+to+Unmask+the+Mesenteric+and+Renal+Vasodilator+Role+of+Endothelin+ETB+Receptorsen_HK
dc.identifier.emailLeung, SWS: swsleung@hku.hken_HK
dc.identifier.emailMan, RYK: rykman@hkucc.hku.hken_HK
dc.identifier.authorityLeung, SWS=rp00235en_HK
dc.identifier.authorityMan, RYK=rp00236en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1097/00005344-200204000-00009en_HK
dc.identifier.pmid11904527-
dc.identifier.scopuseid_2-s2.0-0036196432en_HK
dc.identifier.hkuros73442en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0036196432&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume39en_HK
dc.identifier.issue4en_HK
dc.identifier.spage533en_HK
dc.identifier.epage543en_HK
dc.identifier.isiWOS:000174677900009-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLeung, SWS=24540419500en_HK
dc.identifier.scopusauthoridLim, SL=7404080728en_HK
dc.identifier.scopusauthoridPang, CCY=7201425219en_HK
dc.identifier.scopusauthoridMan, RYK=7004986435en_HK

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