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Article: The combined 5-HT2 receptor and calcium channel inhibitor LU49938 restores endothelium dependent responses in the regenerated endothelium of the porcine coronary artery

TitleThe combined 5-HT2 receptor and calcium channel inhibitor LU49938 restores endothelium dependent responses in the regenerated endothelium of the porcine coronary artery
Authors
Issue Date1995
PublisherOxford University Press. The Journal's web site is located at http://cardiovascres.oxfordjournals.org
Citation
Cardiovascular Research, 1995, v. 29 n. 1, p. 95-101 How to Cite?
AbstractObjective: The aim was to evaluate the effect of the combined 5-hydroxytryptamine-2 (5-HT2) receptor antagonist and calcium channel inhibitor LU49938 ((2S)-5-[N-methyl-N-(n-hexyl)] amino-2-isopropyl-2(3.4.5-trimethoxyphenyl)-valeronitrilhydrochloride) on the endothelium dependent responsiveness of porcine coronary arteries with native and regenerated endothelium. Methods: Male Yorkshire pigs were assigned randomly to one of four groups: (1) controls; (2) pigs receiving LU49938 daily (5 mg·kg-1) for four weeks; (3) pigs undergoing balloon de-endothelialisation of the left anterior descending coronary artery; and (4) pigs undergoing balloon de-endothelialisation and receiving LU49938 daily. At four weeks, quantitative coronary angiography, organ chamber experiments, and morphometric studies of the tissues were performed. Results: Treatment with LU49938 did not affect the endothelium dependent responses in native porcine coronary arteries. Intracoronary injection of serotonin caused significantly greater coronary vasoconstriction in group 3 compared with group 4. The cross sectional area of the intima and media of previously de-endothelialised left anterior descending coronary artery increased significantly in group 3, but not in group 4. In arteries with regenerated endothelium, augmented endothelium dependent contractions were noted not only in response to serotonin, but also in response to platelets, noradrenaline, and endothelin-1. The endothelium dependent relaxations to platelets, serotonin, and UK14304 were impaired in the regenerated endothelium, but not those to adenosine diphosphate and SIN-1. However, following four weeks of treatment with LU49938, the pertussis toxin sensitive endothelium dependent responses were restored. The augmented endothelium dependent contraction to endothelin-1 was not altered by the treatment. Conclusions: Chronic treatment with LU49938 restores endothelium dependent, pertussis toxin sensitive, G protein mediated responses in the regenerated endothelium of the porcine coronary artery, and inhibits the intimal thickening following arterial injury.
Persistent Identifierhttp://hdl.handle.net/10722/171160
ISSN
2015 Impact Factor: 5.465
2015 SCImago Journal Rankings: 2.897

 

DC FieldValueLanguage
dc.contributor.authorPark, SJen_US
dc.contributor.authorLee, JJen_US
dc.contributor.authorKirchengast, Men_US
dc.contributor.authorBoulanger, CMen_US
dc.contributor.authorVanhoutte, PMen_US
dc.date.accessioned2012-10-30T06:12:28Z-
dc.date.available2012-10-30T06:12:28Z-
dc.date.issued1995en_US
dc.identifier.citationCardiovascular Research, 1995, v. 29 n. 1, p. 95-101en_US
dc.identifier.issn0008-6363en_US
dc.identifier.urihttp://hdl.handle.net/10722/171160-
dc.description.abstractObjective: The aim was to evaluate the effect of the combined 5-hydroxytryptamine-2 (5-HT2) receptor antagonist and calcium channel inhibitor LU49938 ((2S)-5-[N-methyl-N-(n-hexyl)] amino-2-isopropyl-2(3.4.5-trimethoxyphenyl)-valeronitrilhydrochloride) on the endothelium dependent responsiveness of porcine coronary arteries with native and regenerated endothelium. Methods: Male Yorkshire pigs were assigned randomly to one of four groups: (1) controls; (2) pigs receiving LU49938 daily (5 mg·kg-1) for four weeks; (3) pigs undergoing balloon de-endothelialisation of the left anterior descending coronary artery; and (4) pigs undergoing balloon de-endothelialisation and receiving LU49938 daily. At four weeks, quantitative coronary angiography, organ chamber experiments, and morphometric studies of the tissues were performed. Results: Treatment with LU49938 did not affect the endothelium dependent responses in native porcine coronary arteries. Intracoronary injection of serotonin caused significantly greater coronary vasoconstriction in group 3 compared with group 4. The cross sectional area of the intima and media of previously de-endothelialised left anterior descending coronary artery increased significantly in group 3, but not in group 4. In arteries with regenerated endothelium, augmented endothelium dependent contractions were noted not only in response to serotonin, but also in response to platelets, noradrenaline, and endothelin-1. The endothelium dependent relaxations to platelets, serotonin, and UK14304 were impaired in the regenerated endothelium, but not those to adenosine diphosphate and SIN-1. However, following four weeks of treatment with LU49938, the pertussis toxin sensitive endothelium dependent responses were restored. The augmented endothelium dependent contraction to endothelin-1 was not altered by the treatment. Conclusions: Chronic treatment with LU49938 restores endothelium dependent, pertussis toxin sensitive, G protein mediated responses in the regenerated endothelium of the porcine coronary artery, and inhibits the intimal thickening following arterial injury.en_US
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://cardiovascres.oxfordjournals.orgen_US
dc.relation.ispartofCardiovascular Researchen_US
dc.subject.meshAdrenergic Alpha-Antagonists - Pharmacologyen_US
dc.subject.meshAngioplasty, Balloonen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBlood Plateletsen_US
dc.subject.meshCalcium Channel Blockers - Pharmacologyen_US
dc.subject.meshCoronary Angiographyen_US
dc.subject.meshCoronary Vessels - Injuries - Pathologyen_US
dc.subject.meshEndothelins - Pharmacologyen_US
dc.subject.meshEndothelium, Vascular - Drug Effects - Injuries - Pathology - Physiologyen_US
dc.subject.meshMaleen_US
dc.subject.meshNorepinephrine - Pharmacologyen_US
dc.subject.meshQuinoxalines - Pharmacologyen_US
dc.subject.meshRandom Allocationen_US
dc.subject.meshRegenerationen_US
dc.subject.meshSerotonin - Pharmacologyen_US
dc.subject.meshSerotonin Antagonists - Pharmacologyen_US
dc.subject.meshSwineen_US
dc.subject.meshTunica Intima - Drug Effects - Pathologyen_US
dc.subject.meshVasoconstriction - Drug Effectsen_US
dc.subject.meshVerapamil - Analogs & Derivatives - Pharmacologyen_US
dc.titleThe combined 5-HT2 receptor and calcium channel inhibitor LU49938 restores endothelium dependent responses in the regenerated endothelium of the porcine coronary arteryen_US
dc.typeArticleen_US
dc.identifier.emailVanhoutte, PM:vanhoutt@hku.hken_US
dc.identifier.authorityVanhoutte, PM=rp00238en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/0008-6363(96)88552-Xen_US
dc.identifier.pmid7895245-
dc.identifier.scopuseid_2-s2.0-0028980167en_US
dc.identifier.volume29en_US
dc.identifier.issue1en_US
dc.identifier.spage95en_US
dc.identifier.epage101en_US
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridPark, SJ=7501828826en_US
dc.identifier.scopusauthoridLee, JJ=7601457545en_US
dc.identifier.scopusauthoridKirchengast, M=7004242148en_US
dc.identifier.scopusauthoridBoulanger, CM=7006599024en_US
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_US

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