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Article: Chronic inhibition of nitric-oxide synthase potentiates endothelium-dependent contractions in the rat aorta by augmenting the expression of cyclooxygenase-2

TitleChronic inhibition of nitric-oxide synthase potentiates endothelium-dependent contractions in the rat aorta by augmenting the expression of cyclooxygenase-2
Authors
Issue Date2010
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, 2010, v. 334 n. 2, p. 373-380 How to Cite?
AbstractAcute inhibition of nitric-oxide synthase (NOS) unmasks the release of endothelium-derived contracting factors (EDCFs). The present study investigated whether chronic inhibition of NOS modulates endothelium-dependent contractions. Eighteen-week-old male Sprague-Dawley rats were treated by daily gavage for 6 weeks with the NOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) (60 mg/ kg) or vehicle (distilled water; 1 ml/kg). Chronic treatment with LNAME increased arterial blood pressure. Isometric tension was measured in aortic rings with or without endothelium. Endotheliumdependent relaxations to acetylcholine and the calcium ionophore 5-(methylamino)-2-[(2R,3R,6S,8S,9R,11R)- 3,9,11-trimethyl-8-[(1S)-1-methyl-2-oxo-2-(1H-pyrrol-2-yl)-ethyl]-1, 7-dioxaspiro[5.5]undec-2-yl]methyl]-4-benzoxazolecarboxylic acid (A23187) were reduced in preparations from L-NAME-treated rats. The reduction in relaxation to A23187 was partially reversed by L-arginine (1 mM). In quiescent aortic rings, A23187 caused contractions in the presence of L-NAME and intact endothelium. The A23187-induced contractions were greater in rings from the L-NAME-treated rats than in those from the control group. These contractions were abolished by the cyclooxygenase (COX)-2 inhibitor N-[2-cyclohexyloxy-4-nitrophenyl] methanesulfonamide (NS-398) and the thromboxane-prostanoid (TP) receptor antagonist 3-((6R)-6-{[(4-chlorophenyl)sulfonyl]amido}-2-methyl-5,6,7,8- tetrahydronaphthalen-1-yl)propanoate (S18886), but not by the COX-1 inhibitor 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC-560). Chronic L-NAME treatment reduced the level of nitric oxide in the plasma but increased COX activity in the aortic rings. Western blotting and immunohistochemical staining showed that endothelial NOS expression was reduced in the aortae of the chronic L-NAME-treated group. COX-1 expression was augmented slightly, whereas COX-2 expression was up-regulated markedly. The TP receptor expression was comparable with control. These experiments demonstrate that chronic NOS inhibition increases endothelium-dependent contractions of the rat aorta by inducing COX-2 expression and augmenting the production of EDCF. Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics.
Persistent Identifierhttp://hdl.handle.net/10722/125256
ISSN
2015 Impact Factor: 3.76
2015 SCImago Journal Rankings: 1.847
ISI Accession Number ID
Funding AgencyGrant Number
Research Grant Council of Hong Kong7681/06M
Funding Information:

This study was supported by the Research Grant Council of Hong Kong [Grant University of Hong Kong 7681/06M].

References

 

DC FieldValueLanguage
dc.contributor.authorQu, Cen_HK
dc.contributor.authorLeung, SWSen_HK
dc.contributor.authorVanhoutte, PMen_HK
dc.contributor.authorMan, RYKen_HK
dc.date.accessioned2010-10-31T11:20:22Z-
dc.date.available2010-10-31T11:20:22Z-
dc.date.issued2010en_HK
dc.identifier.citationJournal Of Pharmacology And Experimental Therapeutics, 2010, v. 334 n. 2, p. 373-380en_HK
dc.identifier.issn0022-3565en_HK
dc.identifier.urihttp://hdl.handle.net/10722/125256-
dc.description.abstractAcute inhibition of nitric-oxide synthase (NOS) unmasks the release of endothelium-derived contracting factors (EDCFs). The present study investigated whether chronic inhibition of NOS modulates endothelium-dependent contractions. Eighteen-week-old male Sprague-Dawley rats were treated by daily gavage for 6 weeks with the NOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) (60 mg/ kg) or vehicle (distilled water; 1 ml/kg). Chronic treatment with LNAME increased arterial blood pressure. Isometric tension was measured in aortic rings with or without endothelium. Endotheliumdependent relaxations to acetylcholine and the calcium ionophore 5-(methylamino)-2-[(2R,3R,6S,8S,9R,11R)- 3,9,11-trimethyl-8-[(1S)-1-methyl-2-oxo-2-(1H-pyrrol-2-yl)-ethyl]-1, 7-dioxaspiro[5.5]undec-2-yl]methyl]-4-benzoxazolecarboxylic acid (A23187) were reduced in preparations from L-NAME-treated rats. The reduction in relaxation to A23187 was partially reversed by L-arginine (1 mM). In quiescent aortic rings, A23187 caused contractions in the presence of L-NAME and intact endothelium. The A23187-induced contractions were greater in rings from the L-NAME-treated rats than in those from the control group. These contractions were abolished by the cyclooxygenase (COX)-2 inhibitor N-[2-cyclohexyloxy-4-nitrophenyl] methanesulfonamide (NS-398) and the thromboxane-prostanoid (TP) receptor antagonist 3-((6R)-6-{[(4-chlorophenyl)sulfonyl]amido}-2-methyl-5,6,7,8- tetrahydronaphthalen-1-yl)propanoate (S18886), but not by the COX-1 inhibitor 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC-560). Chronic L-NAME treatment reduced the level of nitric oxide in the plasma but increased COX activity in the aortic rings. Western blotting and immunohistochemical staining showed that endothelial NOS expression was reduced in the aortae of the chronic L-NAME-treated group. COX-1 expression was augmented slightly, whereas COX-2 expression was up-regulated markedly. The TP receptor expression was comparable with control. These experiments demonstrate that chronic NOS inhibition increases endothelium-dependent contractions of the rat aorta by inducing COX-2 expression and augmenting the production of EDCF. Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics.en_HK
dc.languageengen_HK
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.titleChronic inhibition of nitric-oxide synthase potentiates endothelium-dependent contractions in the rat aorta by augmenting the expression of cyclooxygenase-2en_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-3565&volume=334,No.2&spage=373&epage=380&date=2010&atitle=Chronic+Inhibition+of+Nitric-Oxide+Synthase+Potentiates+Endothelium-Dependent+Contractions+in+the+Rat+Aorta+by+Augmenting+the+Expression+of+Cyclooxygenase-2en_HK
dc.identifier.emailLeung, SWS: swsleung@hku.hken_HK
dc.identifier.emailVanhoutte, PM: vanhoutt@hku.hken_HK
dc.identifier.emailMan, RYK: rykman@hkucc.hku.hken_HK
dc.identifier.authorityLeung, SWS=rp00235en_HK
dc.identifier.authorityVanhoutte, PM=rp00238en_HK
dc.identifier.authorityMan, RYK=rp00236en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1124/jpet.110.167098en_HK
dc.identifier.pmid20444882-
dc.identifier.scopuseid_2-s2.0-77954921263en_HK
dc.identifier.hkuros173859en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77954921263&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume334en_HK
dc.identifier.issue2en_HK
dc.identifier.spage373en_HK
dc.identifier.epage380en_HK
dc.identifier.eissn1521-0103-
dc.identifier.isiWOS:000279990700003-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridQu, C=36673839600en_HK
dc.identifier.scopusauthoridLeung, SWS=24540419500en_HK
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_HK
dc.identifier.scopusauthoridMan, RYK=7004986435en_HK

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