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Article: Oxygen-derived free radicals mediate endothelium-dependent contractions to acetylcholine in aortas from spontaneously hypertensive rats

TitleOxygen-derived free radicals mediate endothelium-dependent contractions to acetylcholine in aortas from spontaneously hypertensive rats
Authors
Issue Date2002
PublisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1
Citation
British Journal Of Pharmacology, 2002, v. 136 n. 1, p. 104-110 How to Cite?
Abstract1. Experiments were designed to investigate whether or not oxygen-derived free radicals mediate endothelium-dependent contractions to acetylcholine in the aorta of spontaneously hypertensive rat (SHR). 2. Isometric tension was measured in aortic rings taken from adult male SHR and Wistar-Kyoto rat (WKY) in the presence of N G-nitro-L-arginine. 3. Endothelium-dependent contractions to acetylcholine were significantly greater in rings from SHR compared to WKY. Oxygen-derived free radicals, generated from xanthine plus xanthine oxidase, induced contractions that were larger in aortas from SHR than from WKY. Contractions to acetylcholine and free radicals were abolished by a selective TP-receptor antagonist, S 18886, and a preferential inhibitor of cyclo-oxygenase-1, valeryl salicylate, but not by a preferential inhibitor of cyclo-oxygenase-2, NS-398. 4. Allopurinol, deferoxamine and the combination of superoxide dismutase plus catalase inhibited the contractions to oxygen-derived free radicals but did not significantly affect those to acetylcholine. In contrast, diethyldithiocarbamic acid, an inhibitor of superoxide dismutase, or Tiron, a scavenger of superoxide anion, reduced endothelium-dependent contractions to acetylcholine in aortas from SHR. The effect of these two drugs was additive. 5. In SHR chronically treated with dimethylthiourea endothelium-dependent contractions to acetylcholine were decreased, and reduced further by acute in vitro exposure to deferoxamine or the combination of superoxide dismutase plus catalase. 6. These results suggest that in the SHR aorta acetylcholine-induced endothelium-dependent contractions involve endothelial superoxide anion production and the subsequent dismutation into hydroxyl radicals and/or hydrogen peroxide. The free radicals activate cyclo-oxygenase-1, most likely to produce endoperoxides. Activation of TP-receptors is required to observe endothelium-dependent contractions to acetylcholine or endothelium-independent contractions in response to free radical generation.
Persistent Identifierhttp://hdl.handle.net/10722/171278
ISSN
2015 Impact Factor: 5.259
2015 SCImago Journal Rankings: 2.368
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYang, Den_US
dc.contributor.authorFélétou, Men_US
dc.contributor.authorBoulanger, CMen_US
dc.contributor.authorWu, HFen_US
dc.contributor.authorLevens, Nen_US
dc.contributor.authorZhang, JNen_US
dc.contributor.authorVanhoutte, PMen_US
dc.date.accessioned2012-10-30T06:13:08Z-
dc.date.available2012-10-30T06:13:08Z-
dc.date.issued2002en_US
dc.identifier.citationBritish Journal Of Pharmacology, 2002, v. 136 n. 1, p. 104-110en_US
dc.identifier.issn0007-1188en_US
dc.identifier.urihttp://hdl.handle.net/10722/171278-
dc.description.abstract1. Experiments were designed to investigate whether or not oxygen-derived free radicals mediate endothelium-dependent contractions to acetylcholine in the aorta of spontaneously hypertensive rat (SHR). 2. Isometric tension was measured in aortic rings taken from adult male SHR and Wistar-Kyoto rat (WKY) in the presence of N G-nitro-L-arginine. 3. Endothelium-dependent contractions to acetylcholine were significantly greater in rings from SHR compared to WKY. Oxygen-derived free radicals, generated from xanthine plus xanthine oxidase, induced contractions that were larger in aortas from SHR than from WKY. Contractions to acetylcholine and free radicals were abolished by a selective TP-receptor antagonist, S 18886, and a preferential inhibitor of cyclo-oxygenase-1, valeryl salicylate, but not by a preferential inhibitor of cyclo-oxygenase-2, NS-398. 4. Allopurinol, deferoxamine and the combination of superoxide dismutase plus catalase inhibited the contractions to oxygen-derived free radicals but did not significantly affect those to acetylcholine. In contrast, diethyldithiocarbamic acid, an inhibitor of superoxide dismutase, or Tiron, a scavenger of superoxide anion, reduced endothelium-dependent contractions to acetylcholine in aortas from SHR. The effect of these two drugs was additive. 5. In SHR chronically treated with dimethylthiourea endothelium-dependent contractions to acetylcholine were decreased, and reduced further by acute in vitro exposure to deferoxamine or the combination of superoxide dismutase plus catalase. 6. These results suggest that in the SHR aorta acetylcholine-induced endothelium-dependent contractions involve endothelial superoxide anion production and the subsequent dismutation into hydroxyl radicals and/or hydrogen peroxide. The free radicals activate cyclo-oxygenase-1, most likely to produce endoperoxides. Activation of TP-receptors is required to observe endothelium-dependent contractions to acetylcholine or endothelium-independent contractions in response to free radical generation.en_US
dc.languageengen_US
dc.publisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1en_US
dc.relation.ispartofBritish Journal of Pharmacologyen_US
dc.subject.meshAcetylcholine - Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAorta, Thoracic - Drug Effects - Metabolism - Physiologyen_US
dc.subject.meshEndothelium, Vascular - Physiologyen_US
dc.subject.meshFree Radical Scavengers - Pharmacologyen_US
dc.subject.meshFree Radicals - Metabolismen_US
dc.subject.meshMaleen_US
dc.subject.meshMuscle Contraction - Drug Effectsen_US
dc.subject.meshMuscle, Smooth, Vascular - Drug Effects - Metabolism - Physiologyen_US
dc.subject.meshOxygen - Metabolismen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Inbred Shren_US
dc.subject.meshRats, Inbred Wkyen_US
dc.subject.meshSpecies Specificityen_US
dc.subject.meshThiourea - Analogs & Derivatives - Pharmacologyen_US
dc.subject.meshVasodilator Agents - Pharmacologyen_US
dc.titleOxygen-derived free radicals mediate endothelium-dependent contractions to acetylcholine in aortas from spontaneously hypertensive ratsen_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.doi10.1038/sj.bjp.0704669-
dc.identifier.pmid11976274-
dc.identifier.scopuseid_2-s2.0-0036264483en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0036264483&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume136en_US
dc.identifier.issue1en_US
dc.identifier.spage104en_US
dc.identifier.epage110en_US
dc.identifier.isiWOS:000175389800013-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridYang, D=7404801018en_US
dc.identifier.scopusauthoridFélétou, M=7006461826en_US
dc.identifier.scopusauthoridBoulanger, CM=7006599024en_US
dc.identifier.scopusauthoridWu, HF=7405583306en_US
dc.identifier.scopusauthoridLevens, N=7006081223en_US
dc.identifier.scopusauthoridZhang, JN=7601344287en_US
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_US

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