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Article: Specific potentiation of endothelium-dependent contractions in SHR by tetrahydrobiopterin

TitleSpecific potentiation of endothelium-dependent contractions in SHR by tetrahydrobiopterin
Authors
Issue Date2003
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://hyper.ahajournals.org/
Citation
Hypertension, 2003, v. 41 n. 1, p. 136-142 How to Cite?
AbstractThis study was designed to determine the effect of pteridines, R- and S-tetrahydrobiopterin, sepiapterin, and dihydrobiopterin on endothelium-dependent contractions to acetylcholine in isolated aortas from spontaneously hypertensive rat and normotensive Wistar-Kyoto rat. The noncumulative addition of redox-active pteridines R- and S-tetrahydrobiopterin (but not the oxidized analogues sepiapterin and dihydrobiopterin) produced a concentration-dependent transient contraction in isolated aortic rings from both normotensive and hypertensive rats. R- and S-tetrahydrobiopterin (but not sepiapterin or dihydrobiopterin) potentiated the endothelium-dependent contractions to acetylcholine but only in aortas from hypertensive rats and in the presence of NG-nitro-L-arginine. In these aortas, the generation of oxygen-derived free radicals by the combination of xanthine plus xanthine oxidase also potentiated the endothelium-dependent contractions to acetylcholine. The presence of R-tetrahydrobiopterin did not alter the characteristics of the endothelium-dependent contractions because they were inhibited by valeryl salicylate, an inhibitor of cyclooxygenase-1, by S 18886, a TP-receptor antagonist or by Tiron, a cell permeable superoxide anion scavenger. However, the contractions to acetylcholine, which are unaffected by the combination of superoxide dismutase and catalase, become significantly inhibited by these two scavengers in the presence of R-tetrahydrobiopterin. In the presence of NG-nitro-L-arginine, R-tetrahydrobiopterin did not affect the contractions to phenylephrine, U 46619, or to oxygen-derived free radicals generated by xanthine plus xanthine oxidase. These results indicate that the production of superoxide by the autoxidation of tetrahydrobiopterin selectively enhances endothelium-dependent contractions in the spontaneously hypertensive rat when nitric oxide synthase is inhibited.
Persistent Identifierhttp://hdl.handle.net/10722/171289
ISSN
2015 Impact Factor: 6.294
2015 SCImago Journal Rankings: 3.702
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYang, Den_US
dc.contributor.authorLevens, Nen_US
dc.contributor.authorZhang, JNen_US
dc.contributor.authorVanhoutte, PMen_US
dc.contributor.authorFélétou, Men_US
dc.date.accessioned2012-10-30T06:13:12Z-
dc.date.available2012-10-30T06:13:12Z-
dc.date.issued2003en_US
dc.identifier.citationHypertension, 2003, v. 41 n. 1, p. 136-142en_US
dc.identifier.issn0194-911Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/171289-
dc.description.abstractThis study was designed to determine the effect of pteridines, R- and S-tetrahydrobiopterin, sepiapterin, and dihydrobiopterin on endothelium-dependent contractions to acetylcholine in isolated aortas from spontaneously hypertensive rat and normotensive Wistar-Kyoto rat. The noncumulative addition of redox-active pteridines R- and S-tetrahydrobiopterin (but not the oxidized analogues sepiapterin and dihydrobiopterin) produced a concentration-dependent transient contraction in isolated aortic rings from both normotensive and hypertensive rats. R- and S-tetrahydrobiopterin (but not sepiapterin or dihydrobiopterin) potentiated the endothelium-dependent contractions to acetylcholine but only in aortas from hypertensive rats and in the presence of NG-nitro-L-arginine. In these aortas, the generation of oxygen-derived free radicals by the combination of xanthine plus xanthine oxidase also potentiated the endothelium-dependent contractions to acetylcholine. The presence of R-tetrahydrobiopterin did not alter the characteristics of the endothelium-dependent contractions because they were inhibited by valeryl salicylate, an inhibitor of cyclooxygenase-1, by S 18886, a TP-receptor antagonist or by Tiron, a cell permeable superoxide anion scavenger. However, the contractions to acetylcholine, which are unaffected by the combination of superoxide dismutase and catalase, become significantly inhibited by these two scavengers in the presence of R-tetrahydrobiopterin. In the presence of NG-nitro-L-arginine, R-tetrahydrobiopterin did not affect the contractions to phenylephrine, U 46619, or to oxygen-derived free radicals generated by xanthine plus xanthine oxidase. These results indicate that the production of superoxide by the autoxidation of tetrahydrobiopterin selectively enhances endothelium-dependent contractions in the spontaneously hypertensive rat when nitric oxide synthase is inhibited.en_US
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://hyper.ahajournals.org/en_US
dc.relation.ispartofHypertensionen_US
dc.subject.meshAcetylcholine - Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAorta - Drug Effects - Enzymology - Physiopathologyen_US
dc.subject.meshBiopterin - Analogs & Derivatives - Pharmacologyen_US
dc.subject.meshCulture Techniquesen_US
dc.subject.meshDithiothreitol - Pharmacologyen_US
dc.subject.meshDose-Response Relationship, Drugen_US
dc.subject.meshDrug Synergismen_US
dc.subject.meshEndothelium, Vascular - Drug Effects - Enzymology - Physiopathologyen_US
dc.subject.meshEnzyme Inhibitors - Pharmacologyen_US
dc.subject.meshHypertension - Enzymology - Metabolism - Physiopathologyen_US
dc.subject.meshNitric Oxide Synthase - Antagonists & Inhibitorsen_US
dc.subject.meshNitroarginine - Pharmacologyen_US
dc.subject.meshPteridines - Pharmacologyen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Inbred Shren_US
dc.subject.meshRats, Inbred Wkyen_US
dc.subject.meshReactive Oxygen Species - Metabolismen_US
dc.subject.meshReducing Agents - Pharmacologyen_US
dc.subject.meshVasoconstriction - Drug Effectsen_US
dc.subject.meshVasodilation - Drug Effectsen_US
dc.titleSpecific potentiation of endothelium-dependent contractions in SHR by tetrahydrobiopterinen_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.doi10.1161/01.HYP.0000047669.93078.A7en_US
dc.identifier.pmid12511543-
dc.identifier.scopuseid_2-s2.0-0037219687en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0037219687&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume41en_US
dc.identifier.issue1en_US
dc.identifier.spage136en_US
dc.identifier.epage142en_US
dc.identifier.isiWOS:000180367000023-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridYang, D=7404801018en_US
dc.identifier.scopusauthoridLevens, N=7006081223en_US
dc.identifier.scopusauthoridZhang, JN=7601344287en_US
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_US
dc.identifier.scopusauthoridFélétou, M=7006461826en_US

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