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Article: Activation of nicotinic receptors can contribute to endothelium-dependent relaxations to acetylcholine in the rat aorta

TitleActivation of nicotinic receptors can contribute to endothelium-dependent relaxations to acetylcholine in the rat aorta
Authors
Issue Date2012
PublisherAmerican Society for Pharmacology and Experimental Therapeutics. The Journal's web site is located at http://jpet.aspetjournals.org
Citation
Journal Of Pharmacology And Experimental Therapeutics, 2012, v. 341 n. 3, p. 756-763 How to Cite?
AbstractAcetylcholine causes endothelium-dependent relaxations in the rat aorta. Both muscarinic acetylcholine receptors (mAChRs) and nicotinic acetylcholine receptors (nAChRs) are expressed in endothelial cells. It is generally accepted that mAChRs are responsible for the endothelium-dependent relaxations evoked by acetylcholine. The present study was designed to investigate whether nAChRs can also be involved in such responses evoked by the cholinergic transmitter. Rings with or without endothelium of aortae of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive rats were suspended in organ chambers for the measurement of isometric tension. In WKY aortae the muscarinic antagonist atropine abolished the relaxations to increasing concentrations of acetylcholine, confirming that mAChRs are responsible mainly for the response under control conditions. In SHR aortae, atropine caused only partial inhibition of the endothelium-dependent relaxations to acetylcholine; the remaining decreases in tension were inhibited by the nicotinic antagonist mecamylamine, which did not significantly affect the response in the absence of atropine in either SHR or WKY preparations. Thus, when mAChRs are inhibited, nAChRs mediate relaxation to the cholinergic transmitter in the SHR but not the WKY aorta. Nicotine, a direct agonist of the nicotinic receptor, induced endothelium-dependent relaxations in both SHR and WKY rats via the activation of α7-nAChRs, but not by mecamylamine-sensitive nicotinic receptors (α3 subtype). The acetylcholine-induced, atropine-insensitive relaxations and those to nicotine both involve the phosphatidylinositol 3-kinase/AKT pathway. The present study demonstrates that the activation of nAChRs can contribute to acetylcholine-induced, endothelium-dependent relaxations in the aortae of hypertensive animals and suggests that these receptors may contribute to the endothelium-dependent regulation of vascular tone. Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics.
Persistent Identifierhttp://hdl.handle.net/10722/149122
ISSN
2015 Impact Factor: 3.76
2015 SCImago Journal Rankings: 1.847
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grant Council780410M
Research Centre of Heart, Brain, Hormone and Healthy Aging of the University of Hong Kong
World Class University
Ministry of Education, Science, and Technology, South KoreaR31-20029
Funding Information:

This work was supported in part by the Hong Kong Research Grant Council [Grant 780410M]; the Research Centre of Heart, Brain, Hormone and Healthy Aging of the University of Hong Kong; and the World Class University program funded by the Ministry of Education, Science, and Technology, South Korea [Grant R31-20029].

References

 

DC FieldValueLanguage
dc.contributor.authorZou, Qen_HK
dc.contributor.authorLeung, SWSen_HK
dc.contributor.authorVanhoutte, PMen_HK
dc.date.accessioned2012-06-22T06:24:29Z-
dc.date.available2012-06-22T06:24:29Z-
dc.date.issued2012en_HK
dc.identifier.citationJournal Of Pharmacology And Experimental Therapeutics, 2012, v. 341 n. 3, p. 756-763en_HK
dc.identifier.issn0022-3565en_HK
dc.identifier.urihttp://hdl.handle.net/10722/149122-
dc.description.abstractAcetylcholine causes endothelium-dependent relaxations in the rat aorta. Both muscarinic acetylcholine receptors (mAChRs) and nicotinic acetylcholine receptors (nAChRs) are expressed in endothelial cells. It is generally accepted that mAChRs are responsible for the endothelium-dependent relaxations evoked by acetylcholine. The present study was designed to investigate whether nAChRs can also be involved in such responses evoked by the cholinergic transmitter. Rings with or without endothelium of aortae of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive rats were suspended in organ chambers for the measurement of isometric tension. In WKY aortae the muscarinic antagonist atropine abolished the relaxations to increasing concentrations of acetylcholine, confirming that mAChRs are responsible mainly for the response under control conditions. In SHR aortae, atropine caused only partial inhibition of the endothelium-dependent relaxations to acetylcholine; the remaining decreases in tension were inhibited by the nicotinic antagonist mecamylamine, which did not significantly affect the response in the absence of atropine in either SHR or WKY preparations. Thus, when mAChRs are inhibited, nAChRs mediate relaxation to the cholinergic transmitter in the SHR but not the WKY aorta. Nicotine, a direct agonist of the nicotinic receptor, induced endothelium-dependent relaxations in both SHR and WKY rats via the activation of α7-nAChRs, but not by mecamylamine-sensitive nicotinic receptors (α3 subtype). The acetylcholine-induced, atropine-insensitive relaxations and those to nicotine both involve the phosphatidylinositol 3-kinase/AKT pathway. The present study demonstrates that the activation of nAChRs can contribute to acetylcholine-induced, endothelium-dependent relaxations in the aortae of hypertensive animals and suggests that these receptors may contribute to the endothelium-dependent regulation of vascular tone. Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics.en_HK
dc.languageengen_US
dc.publisherAmerican Society for Pharmacology and Experimental Therapeutics. The Journal's web site is located at http://jpet.aspetjournals.orgen_HK
dc.relation.ispartofJournal of Pharmacology and Experimental Therapeuticsen_HK
dc.subject.meshAcetylcholine - pharmacology-
dc.subject.meshEndothelium, Vascular - physiology-
dc.subject.meshMuscle Relaxation - physiology-
dc.subject.meshMuscle, Smooth, Vascular - physiology-
dc.subject.meshReceptors, Nicotinic - metabolism-
dc.titleActivation of nicotinic receptors can contribute to endothelium-dependent relaxations to acetylcholine in the rat aortaen_HK
dc.typeArticleen_HK
dc.identifier.emailLeung, SWS: swsleung@hku.hken_HK
dc.identifier.emailVanhoutte, PM: vanhoutt@hku.hken_HK
dc.identifier.authorityLeung, SWS=rp00235en_HK
dc.identifier.authorityVanhoutte, PM=rp00238en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1124/jpet.112.192229en_HK
dc.identifier.pmid22427701-
dc.identifier.scopuseid_2-s2.0-84861534729en_HK
dc.identifier.hkuros199998en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84861534729&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume341en_HK
dc.identifier.issue3en_HK
dc.identifier.spage756en_HK
dc.identifier.epage763en_HK
dc.identifier.eissn1521-0103-
dc.identifier.isiWOS:000304445000021-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridZou, Q=55232839300en_HK
dc.identifier.scopusauthoridLeung, SWS=24540419500en_HK
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_HK

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