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Conference Paper: Endothelial NOS-independent release of nitric oxide in the aorta of the spontaneously hypertensive rat

TitleEndothelial NOS-independent release of nitric oxide in the aorta of the spontaneously hypertensive rat
Authors
Issue Date2011
PublisherChinese Journal of Pharmacology and Toxicology Editorial Board.
Citation
2011年中国药理学会第十一次全国学术大会'药物临床研究与评价专题研讨会', 山东省济南市, 2011年9月22-25日. In Chinese Journal of Pharmacology and Toxicology, 2011, v. 25 增刊, p. 140 How to Cite?
AbstractOBJECTIVE: Preliminary experiments showed that in the aorta of male spontaneously hypertensive (SHR), but not in that of normotensive Wistar-Kyoto (WKY) rats, contraction to phenylephrine was inhibited by an unknown endothelium-derived factor despite the presence of indomethacin [inhibitor of cyclooxygenase] and L-NAME [inhibitor of nitric oxide synthase (NOS)]. The present study aimed to identify the mechanism underlying this endothelium-dependent inhibition in the SHR aorta. METHODS: Aortic rings, with and without endothelium, of male SHR and WKY [age 12 to 20 weeks (young) or 38 to 48 weeks (adult)] were suspended in organ chambers for the measurement of isometric tension. The preparations were incubated with indomethacin (10-5 mol•L-1) and L-NAME (10-4 mol•L-1) to eliminate the effect of endogenous prostanoids and nitric oxide (NO) produced by NOS, respectively. RESULTS: Contractions to phenylephrine were smaller in SHR aorta with than in those without endothelium. The inhibitory effect of the endothelium was larger in preparations from adult than those from young SHR. The endothelium-dependent difference in contraction to phenylephrine was abolished by oxyhemoglobin (nitric oxide scavenger), carboxy-PTIO (nitric oxide scavenger) or ODQ (inhibitor of soluble guanylyl cyclase), and partly prevented by diphenyleneiodonium (inhibitor of cytochrome P450 reductase) or clotrimazole (inhibitor of cytochrome P450). On the other hand, phenylephrine-induced contraction in adult WKY aortic rings with and without endothelium was not affected by either carboxy-PTIO or ODQ. CONCLUSION: In the SHR aorta, there is an endothelium-dependent release of nitric oxide which is not produced by NOS but by cytochrome P450 reductase and cytochrome P450. Nitrate and nitrite are the likely sources of this NOS-independent nitric oxide. NOS-independent nitric oxide release is seen only in preparations from hypertensive animals and is increased with aging when endothelial dysfunction develops.
DescriptionHKPS / CPS Joint Meeting (中国药理学会-香港药理学会双边学术交流)
Persistent Identifierhttp://hdl.handle.net/10722/149238
ISSN
2015 SCImago Journal Rankings: 0.119

 

DC FieldValueLanguage
dc.contributor.authorZhao, Y-
dc.contributor.authorLeung, SWS-
dc.contributor.authorVanhoutte, PM-
dc.date.accessioned2012-06-22T06:32:03Z-
dc.date.available2012-06-22T06:32:03Z-
dc.date.issued2011-
dc.identifier.citation2011年中国药理学会第十一次全国学术大会'药物临床研究与评价专题研讨会', 山东省济南市, 2011年9月22-25日. In Chinese Journal of Pharmacology and Toxicology, 2011, v. 25 增刊, p. 140-
dc.identifier.issn1000-3002-
dc.identifier.urihttp://hdl.handle.net/10722/149238-
dc.descriptionHKPS / CPS Joint Meeting (中国药理学会-香港药理学会双边学术交流)-
dc.description.abstractOBJECTIVE: Preliminary experiments showed that in the aorta of male spontaneously hypertensive (SHR), but not in that of normotensive Wistar-Kyoto (WKY) rats, contraction to phenylephrine was inhibited by an unknown endothelium-derived factor despite the presence of indomethacin [inhibitor of cyclooxygenase] and L-NAME [inhibitor of nitric oxide synthase (NOS)]. The present study aimed to identify the mechanism underlying this endothelium-dependent inhibition in the SHR aorta. METHODS: Aortic rings, with and without endothelium, of male SHR and WKY [age 12 to 20 weeks (young) or 38 to 48 weeks (adult)] were suspended in organ chambers for the measurement of isometric tension. The preparations were incubated with indomethacin (10-5 mol•L-1) and L-NAME (10-4 mol•L-1) to eliminate the effect of endogenous prostanoids and nitric oxide (NO) produced by NOS, respectively. RESULTS: Contractions to phenylephrine were smaller in SHR aorta with than in those without endothelium. The inhibitory effect of the endothelium was larger in preparations from adult than those from young SHR. The endothelium-dependent difference in contraction to phenylephrine was abolished by oxyhemoglobin (nitric oxide scavenger), carboxy-PTIO (nitric oxide scavenger) or ODQ (inhibitor of soluble guanylyl cyclase), and partly prevented by diphenyleneiodonium (inhibitor of cytochrome P450 reductase) or clotrimazole (inhibitor of cytochrome P450). On the other hand, phenylephrine-induced contraction in adult WKY aortic rings with and without endothelium was not affected by either carboxy-PTIO or ODQ. CONCLUSION: In the SHR aorta, there is an endothelium-dependent release of nitric oxide which is not produced by NOS but by cytochrome P450 reductase and cytochrome P450. Nitrate and nitrite are the likely sources of this NOS-independent nitric oxide. NOS-independent nitric oxide release is seen only in preparations from hypertensive animals and is increased with aging when endothelial dysfunction develops.-
dc.languageeng-
dc.publisherChinese Journal of Pharmacology and Toxicology Editorial Board.-
dc.relation.ispartofChinese Journal of Pharmacology and Toxicology-
dc.relation.ispartof中国药理学与毒理学杂誌-
dc.titleEndothelial NOS-independent release of nitric oxide in the aorta of the spontaneously hypertensive rat-
dc.typeConference_Paper-
dc.identifier.emailLeung, SWS: swsleung@hku.hk-
dc.identifier.emailVanhoutte, PM: vanhoutt@hku.hk-
dc.identifier.authorityLeung, SWS=rp00235-
dc.identifier.authorityVanhoutte, PM=rp00238-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros200019-
dc.identifier.volume25-
dc.identifier.issue增刊-
dc.identifier.spage140-
dc.identifier.epage140-
dc.publisher.placeBeijing, China-

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