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Article: Potentiation of EDHF-mediated relaxation by chloride channel blockers

TitlePotentiation of EDHF-mediated relaxation by chloride channel blockers
Authors
Keywordschloride channels
endothelium-derived hyperpolarizing factor
potassium channels
Issue Date2010
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/aps/index.html
Citation
Acta Pharmacologica Sinica, 2010, v. 31 n. 10, p. 1303-1311 How to Cite?
AbstractAim: To investigate the involvement of Cl channels in endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation in rat mesenteric arteries. Methods: Cl channel and K ir channel activities were studied using whole-cell patch clamping in rat mesenteric arterial smooth muscle cells. Isometric tension of arterial rings was measured in organ chambers. Results: The volume-activated Cl current in rat mesenteric arterial smooth muscle cells was abolished by Cl channel blockers NPPB or DIDS. The EDHF-mediated vasorelaxation was potentiated by NPPB and DIDS. The EDHF response was diminished by a combination of apamin and charybdotoxin, which agreed with the hypothesis that EDHF response involves the release of K + via the Ca 2+-activated K + channels in endothelial cells. The elevation of K + concentration in bathing solution from 1.2 mmol/L to 11.2 mmol/L induced an arterial relaxation, which was abolished by the combination of BaCl 2 and ouabain. It is consistent to the hypothesis that K + activates K + /Na +-ATPase and inward rectifier K + (K ir) channels, leading to the hyperpolarization and relaxation of vascular smooth muscle. The K +-induced relaxation was augmented by NPPB, DIDS, or withdrawal of Cl from the bathing solution, which could be reversed by BaCl 2, but not ouabain. The potentiating effect of Cl channel blockers on K +-induced relaxation was probably due to the interaction between Cl channels and K ir channels. Moreover, the K +-induced relaxation was potentiated when the arteries were incubated in hyperosmotic solution, which is known to inhibit volume-activated Cl channels.Conclusion:The inhibition of Cl channels, particularly the volume-activated Cl channels, may potentiate the EDHF-induced vasorelaxation through the K ir channels. © 2010 CPS and SIMM All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/137119
ISSN
2014 Impact Factor: 2.912
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong SAR769607
University of Hong Kong
Funding Information:

This work was supported by the RGC Earmarked Grants of Hong Kong SAR (project code: 769607), and the Seed Funding for Basic Research Program of the University of Hong Kong.

References

 

DC FieldValueLanguage
dc.contributor.authorYang, Cen_HK
dc.contributor.authorKwan, YWen_HK
dc.contributor.authorChan, SWen_HK
dc.contributor.authorLee, SMYen_HK
dc.contributor.authorLeung, GPHen_HK
dc.date.accessioned2011-08-19T03:19:38Z-
dc.date.available2011-08-19T03:19:38Z-
dc.date.issued2010en_HK
dc.identifier.citationActa Pharmacologica Sinica, 2010, v. 31 n. 10, p. 1303-1311en_HK
dc.identifier.issn1671-4083en_HK
dc.identifier.urihttp://hdl.handle.net/10722/137119-
dc.description.abstractAim: To investigate the involvement of Cl channels in endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation in rat mesenteric arteries. Methods: Cl channel and K ir channel activities were studied using whole-cell patch clamping in rat mesenteric arterial smooth muscle cells. Isometric tension of arterial rings was measured in organ chambers. Results: The volume-activated Cl current in rat mesenteric arterial smooth muscle cells was abolished by Cl channel blockers NPPB or DIDS. The EDHF-mediated vasorelaxation was potentiated by NPPB and DIDS. The EDHF response was diminished by a combination of apamin and charybdotoxin, which agreed with the hypothesis that EDHF response involves the release of K + via the Ca 2+-activated K + channels in endothelial cells. The elevation of K + concentration in bathing solution from 1.2 mmol/L to 11.2 mmol/L induced an arterial relaxation, which was abolished by the combination of BaCl 2 and ouabain. It is consistent to the hypothesis that K + activates K + /Na +-ATPase and inward rectifier K + (K ir) channels, leading to the hyperpolarization and relaxation of vascular smooth muscle. The K +-induced relaxation was augmented by NPPB, DIDS, or withdrawal of Cl from the bathing solution, which could be reversed by BaCl 2, but not ouabain. The potentiating effect of Cl channel blockers on K +-induced relaxation was probably due to the interaction between Cl channels and K ir channels. Moreover, the K +-induced relaxation was potentiated when the arteries were incubated in hyperosmotic solution, which is known to inhibit volume-activated Cl channels.Conclusion:The inhibition of Cl channels, particularly the volume-activated Cl channels, may potentiate the EDHF-induced vasorelaxation through the K ir channels. © 2010 CPS and SIMM All rights reserved.en_HK
dc.languageeng-
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/aps/index.htmlen_HK
dc.relation.ispartofActa Pharmacologica Sinicaen_HK
dc.subjectchloride channelsen_HK
dc.subjectendothelium-derived hyperpolarizing factoren_HK
dc.subjectpotassium channelsen_HK
dc.subject.mesh4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid - pharmacology-
dc.subject.meshChloride Channels - antagonists and inhibitors-
dc.subject.meshEndothelium-Dependent Relaxing Factors - physiology-
dc.subject.meshMesenteric Arteries - drug effects - physiology-
dc.subject.meshNitrobenzoates - pharmacology-
dc.titlePotentiation of EDHF-mediated relaxation by chloride channel blockersen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1671-4083&volume=31&spage=1303&epage=1311&date=2010&atitle=Potentiation+of+EDHF-mediated+relaxation+by+chloride+channel+blockers-
dc.identifier.emailLeung, GPH: gphleung@hkucc.hku.hken_HK
dc.identifier.authorityLeung, GPH=rp00234en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/aps.2010.157en_HK
dc.identifier.pmid20835269en_HK
dc.identifier.scopuseid_2-s2.0-77957735127en_HK
dc.identifier.hkuros189176-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77957735127&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume31en_HK
dc.identifier.issue10en_HK
dc.identifier.spage1303en_HK
dc.identifier.epage1311en_HK
dc.identifier.isiWOS:000283398200008-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridYang, C=36674302100en_HK
dc.identifier.scopusauthoridKwan, YW=7005662153en_HK
dc.identifier.scopusauthoridChan, SW=7404255670en_HK
dc.identifier.scopusauthoridLee, SMY=35233892600en_HK
dc.identifier.scopusauthoridLeung, GPH=35963668200en_HK

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