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Article: Impaired endothelium-dependent relaxation to aggregating platelets and related vasoactive substances in porcine coronary arteries in hypercholesterolemia and atherosclerosis

TitleImpaired endothelium-dependent relaxation to aggregating platelets and related vasoactive substances in porcine coronary arteries in hypercholesterolemia and atherosclerosis
Authors
Issue Date1989
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://circres.ahajournals.org
Citation
Circulation Research, 1989, v. 64 n. 5, p. 900-914 How to Cite?
AbstractVasoconstrictor responses are augmented in porcine coronary arteries in hypercholesterolemia and atherosclerosis, leading to an occurrence of coronary vasospasm in the latter condition. The role of the endothelium in the vascular hyperreactivity in hypercholesterolemic and atherosclerotic coronary arteries was examined, particularly in response to aggregating platelets and related vasoactive substances. Male Yorkshire pigs underwent balloon endothelial denudation of the left anterior descending coronary artery (LAD) and 2% high-cholesterol feeding for 10 weeks. Electron microscopic examination demonstrated a full lining of endothelial cells in the LAD and the left circumflex coronary artery (LCX). Endothelium-dependent responses were examined in vitro. In cholesterol-fed animals, endothelium-dependent relaxations to aggregating platelets, serotonin, ADP, bradykinin, thrombin, and the calcium ionophore A23187 were depressed in LAD (atherosclerosis), while the relaxations to aggregating platelets, serotonin and ADP were depressed in LCX (hypercholesterolemia). Serotonin-induced contractions were endothelium-dependently augmented in atherosclerotic LAD; the endothelium-dependent component of the contractions was inhibited by blockers of cyclooxygenase. Bioassay studies demonstrated a depressed release of endothelium-derived relaxing factor(s) from the atherosclerotic LAD in response to serotonin. These experiments indicate that the endothelium-dependent relaxations to aggregating platelets and related vasoactive substances are severely impaired in atherosclerosis and moderately impaired in hypercholesterolemia. Since coronary atherosclerosis was induced by a combination of balloon endothelial injury (and regeneration) and high-cholesterol feeding in this study, the combined effects of those factors must account for the severely impaired responses in atherosclerosis. The depressed release of the endothelium-derived relaxing factor(s) and the concomitant release of vasoconstrictor product(s) of cyclooxygenase appear to be responsible for the impaired relaxations.
Persistent Identifierhttp://hdl.handle.net/10722/170957
ISSN
2015 Impact Factor: 11.551
2015 SCImago Journal Rankings: 5.755
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorShimokawa, Hen_US
dc.contributor.authorVanhoutte, PMen_US
dc.date.accessioned2012-10-30T06:11:36Z-
dc.date.available2012-10-30T06:11:36Z-
dc.date.issued1989en_US
dc.identifier.citationCirculation Research, 1989, v. 64 n. 5, p. 900-914en_US
dc.identifier.issn0009-7330en_US
dc.identifier.urihttp://hdl.handle.net/10722/170957-
dc.description.abstractVasoconstrictor responses are augmented in porcine coronary arteries in hypercholesterolemia and atherosclerosis, leading to an occurrence of coronary vasospasm in the latter condition. The role of the endothelium in the vascular hyperreactivity in hypercholesterolemic and atherosclerotic coronary arteries was examined, particularly in response to aggregating platelets and related vasoactive substances. Male Yorkshire pigs underwent balloon endothelial denudation of the left anterior descending coronary artery (LAD) and 2% high-cholesterol feeding for 10 weeks. Electron microscopic examination demonstrated a full lining of endothelial cells in the LAD and the left circumflex coronary artery (LCX). Endothelium-dependent responses were examined in vitro. In cholesterol-fed animals, endothelium-dependent relaxations to aggregating platelets, serotonin, ADP, bradykinin, thrombin, and the calcium ionophore A23187 were depressed in LAD (atherosclerosis), while the relaxations to aggregating platelets, serotonin and ADP were depressed in LCX (hypercholesterolemia). Serotonin-induced contractions were endothelium-dependently augmented in atherosclerotic LAD; the endothelium-dependent component of the contractions was inhibited by blockers of cyclooxygenase. Bioassay studies demonstrated a depressed release of endothelium-derived relaxing factor(s) from the atherosclerotic LAD in response to serotonin. These experiments indicate that the endothelium-dependent relaxations to aggregating platelets and related vasoactive substances are severely impaired in atherosclerosis and moderately impaired in hypercholesterolemia. Since coronary atherosclerosis was induced by a combination of balloon endothelial injury (and regeneration) and high-cholesterol feeding in this study, the combined effects of those factors must account for the severely impaired responses in atherosclerosis. The depressed release of the endothelium-derived relaxing factor(s) and the concomitant release of vasoconstrictor product(s) of cyclooxygenase appear to be responsible for the impaired relaxations.en_US
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://circres.ahajournals.orgen_US
dc.relation.ispartofCirculation Researchen_US
dc.subject.meshAdenosine Diphosphate - Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBiological Factors - Secretionen_US
dc.subject.meshBradykinin - Pharmacologyen_US
dc.subject.meshCalcium - Pharmacologyen_US
dc.subject.meshCoronary Disease - Physiopathologyen_US
dc.subject.meshCoronary Vessels - Physiopathologyen_US
dc.subject.meshCyclooxygenase Inhibitorsen_US
dc.subject.meshEndothelium, Vascular - Drug Effects - Physiopathologyen_US
dc.subject.meshHypercholesterolemia - Physiopathologyen_US
dc.subject.meshMaleen_US
dc.subject.meshNitric Oxideen_US
dc.subject.meshPlatelet Aggregationen_US
dc.subject.meshSerotonin - Pharmacologyen_US
dc.subject.meshSwineen_US
dc.subject.meshThrombin - Pharmacologyen_US
dc.titleImpaired endothelium-dependent relaxation to aggregating platelets and related vasoactive substances in porcine coronary arteries in hypercholesterolemia and atherosclerosisen_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.pmid2495869-
dc.identifier.scopuseid_2-s2.0-0024590132en_US
dc.identifier.volume64en_US
dc.identifier.issue5en_US
dc.identifier.spage900en_US
dc.identifier.epage914en_US
dc.identifier.isiWOS:A1989U428000006-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridShimokawa, H=16684837100en_US
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_US

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