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Potentiation of EDHF-mediated relaxation by chloride channel blockers
Yang C.4; Kwan Y.-W.2; Chan S.-W.3; Lee S.M.-Y.1; Leung G.P.-H.4
2010-10-01
Source PublicationActa Pharmacologica Sinica
ISSN16714083 17457254
Volume31Issue:10Pages:1303-1311
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-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.
Keywordchloride channels endothelium-derived hyperpolarizing factor potassium channels
DOI10.1038/aps.2010.157
URLView the original
Language英語
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被引频次[WOS]:5   [WOS记录]     [WOS相关记录]
Document TypeJournal article
专题University of Macau
Affiliation1.University of Macau
2.Chinese University of Hong Kong
3.Hong Kong Polytechnic University
4.The University of Hong Kong
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Yang C.,Kwan Y.-W.,Chan S.-W.,et al. Potentiation of EDHF-mediated relaxation by chloride channel blockers[J]. Acta Pharmacologica Sinica,2010,31(10):1303-1311.
APA Yang C.,Kwan Y.-W.,Chan S.-W.,Lee S.M.-Y.,&Leung G.P.-H..(2010).Potentiation of EDHF-mediated relaxation by chloride channel blockers.Acta Pharmacologica Sinica,31(10),1303-1311.
MLA Yang C.,et al."Potentiation of EDHF-mediated relaxation by chloride channel blockers".Acta Pharmacologica Sinica 31.10(2010):1303-1311.
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