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Article: An endothelium-derived hyperpolarizing factor distinct from NO and prostacyclin is a major endothelium-dependent vasodilator in resistance vessels of wild-type and endothelial NO synthase knockout mice

TitleAn endothelium-derived hyperpolarizing factor distinct from NO and prostacyclin is a major endothelium-dependent vasodilator in resistance vessels of wild-type and endothelial NO synthase knockout mice
Authors
Issue Date2000
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings Of The National Academy Of Sciences Of The United States Of America, 2000, v. 97 n. 17, p. 9747-9752 How to Cite?
AbstractIn addition to nitric oxide (NO) and prostacyclin (PGI2), the endothelium generates the endothelium-derived hyperpolarizing factor (EDHF). We set out to determine whether an EDHF-like response can be detected in wild-type (WT) and endothelial NO synthase knockout mice (eNOS -/-) mice. Vasodilator responses to endothelium-dependent agonists were determined in vivo and in vitro. In vivo, bradykinin induced a pronounced, dose-dependent decrease in mean arterial pressure (MAP) which did not differ between WT and eNOS -/- mice and was unaffected by treatment with Nω-nitro-L-arginine methyl ester and diclofenac. In the saline-perfused hindlimb of WT and eNOS -/- mice, marked Nω-nitro-L-arginine (L-NA, 300 μmol/liter)- and diclofenac-insensitive vasodilations in response to both bradykinin and acetylcholine (ACh) were observed, which were more pronounced than the agonist-induced vasodilation in the hindlimb of WT in the absence of L-NA. This endothelium-dependent, NO/PGI2-independent vasodilatation was sensitive to KCl (40 mM) and to the combination of apamin and charybdotoxin. Gap junction inhibitors (18a-glycyrrhetinic acid, octanol, heptanol) and CB-1 cannabinoid-receptor agonists (Δ9-tetrahydrocannabinol, HU210) impaired EDHF-mediated vasodilation, whereas inhibition of cytochrome P450 enzymes, soluble guanylyl cyclase, or adenosine receptors had no effect on EDHF-mediated responses. These results demonstrate that in murine resistance vessels the predominant agonist-induced endothelium-dependent vasodilation in vivo and in vitro is not mediated by NO, PGI2, or a cytochrome P450 metabolite, but by an EDHF-like principle that requires functional gap junctions.
Persistent Identifierhttp://hdl.handle.net/10722/171252
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorBrandes, RPen_US
dc.contributor.authorSchmitzWinnenthal, FHen_US
dc.contributor.authorFélétou, Men_US
dc.contributor.authorGödecke, Aen_US
dc.contributor.authorHuang, PLen_US
dc.contributor.authorVanhoutte, PMen_US
dc.contributor.authorFleming, Ien_US
dc.contributor.authorBusse, Ren_US
dc.date.accessioned2012-10-30T06:12:58Z-
dc.date.available2012-10-30T06:12:58Z-
dc.date.issued2000en_US
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 2000, v. 97 n. 17, p. 9747-9752en_US
dc.identifier.issn0027-8424en_US
dc.identifier.urihttp://hdl.handle.net/10722/171252-
dc.description.abstractIn addition to nitric oxide (NO) and prostacyclin (PGI2), the endothelium generates the endothelium-derived hyperpolarizing factor (EDHF). We set out to determine whether an EDHF-like response can be detected in wild-type (WT) and endothelial NO synthase knockout mice (eNOS -/-) mice. Vasodilator responses to endothelium-dependent agonists were determined in vivo and in vitro. In vivo, bradykinin induced a pronounced, dose-dependent decrease in mean arterial pressure (MAP) which did not differ between WT and eNOS -/- mice and was unaffected by treatment with Nω-nitro-L-arginine methyl ester and diclofenac. In the saline-perfused hindlimb of WT and eNOS -/- mice, marked Nω-nitro-L-arginine (L-NA, 300 μmol/liter)- and diclofenac-insensitive vasodilations in response to both bradykinin and acetylcholine (ACh) were observed, which were more pronounced than the agonist-induced vasodilation in the hindlimb of WT in the absence of L-NA. This endothelium-dependent, NO/PGI2-independent vasodilatation was sensitive to KCl (40 mM) and to the combination of apamin and charybdotoxin. Gap junction inhibitors (18a-glycyrrhetinic acid, octanol, heptanol) and CB-1 cannabinoid-receptor agonists (Δ9-tetrahydrocannabinol, HU210) impaired EDHF-mediated vasodilation, whereas inhibition of cytochrome P450 enzymes, soluble guanylyl cyclase, or adenosine receptors had no effect on EDHF-mediated responses. These results demonstrate that in murine resistance vessels the predominant agonist-induced endothelium-dependent vasodilation in vivo and in vitro is not mediated by NO, PGI2, or a cytochrome P450 metabolite, but by an EDHF-like principle that requires functional gap junctions.en_US
dc.languageengen_US
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_US
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.subject.meshAcetylcholine - Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshArteries - Drug Effects - Physiologyen_US
dc.subject.meshBiological Factors - Metabolismen_US
dc.subject.meshBlood Pressure - Drug Effectsen_US
dc.subject.meshBradykinin - Pharmacologyen_US
dc.subject.meshCytochrome P-450 Enzyme System - Antagonists & Inhibitors - Metabolismen_US
dc.subject.meshDiclofenac - Pharmacologyen_US
dc.subject.meshEndothelium, Vascular - Drug Effects - Enzymology - Metabolismen_US
dc.subject.meshEpoprostenol - Metabolismen_US
dc.subject.meshGap Junctions - Drug Effects - Physiologyen_US
dc.subject.meshGene Deletionen_US
dc.subject.meshHindlimb - Blood Supply - Drug Effectsen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred C57blen_US
dc.subject.meshMice, Knockouten_US
dc.subject.meshNg-Nitroarginine Methyl Ester - Pharmacologyen_US
dc.subject.meshNitric Oxide - Metabolismen_US
dc.subject.meshNitric Oxide Synthase - Antagonists & Inhibitors - Deficiency - Genetics - Metabolismen_US
dc.subject.meshNitroarginine - Pharmacologyen_US
dc.subject.meshNitroprusside - Pharmacologyen_US
dc.subject.meshPerfusionen_US
dc.subject.meshPotassium Channel Blockersen_US
dc.subject.meshPotassium Channels - Metabolismen_US
dc.subject.meshReceptors, Cannabinoiden_US
dc.subject.meshReceptors, Drug - Antagonists & Inhibitors - Metabolismen_US
dc.subject.meshVasodilation - Drug Effectsen_US
dc.subject.meshVasodilator Agents - Metabolism - Pharmacologyen_US
dc.titleAn endothelium-derived hyperpolarizing factor distinct from NO and prostacyclin is a major endothelium-dependent vasodilator in resistance vessels of wild-type and endothelial NO synthase knockout miceen_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.doi10.1073/pnas.97.17.9747-
dc.identifier.pmid10944233-
dc.identifier.scopuseid_2-s2.0-0034662862en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0034662862&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume97en_US
dc.identifier.issue17en_US
dc.identifier.spage9747en_US
dc.identifier.epage9752en_US
dc.identifier.isiWOS:000088840500074-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridBrandes, RP=35428991000en_US
dc.identifier.scopusauthoridSchmitzWinnenthal, FH=36108795300en_US
dc.identifier.scopusauthoridFélétou, M=7006461826en_US
dc.identifier.scopusauthoridGödecke, A=7003787708en_US
dc.identifier.scopusauthoridHuang, PL=7403659318en_US
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_US
dc.identifier.scopusauthoridFleming, I=7102053742en_US
dc.identifier.scopusauthoridBusse, R=7102661981en_US

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