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Conference Paper: Up-regulation of heme oxygenase-1 improves endothelial function in the spontaneous hypertensive rat

TitleUp-regulation of heme oxygenase-1 improves endothelial function in the spontaneous 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. 138 How to Cite?
AbstractOBJECTIVE: Heme oxygenase (HO) attenuates the production of reactive oxygen species (ROS) by its ability to degrade heme and produce carbon monoxide (CO), biliverdin/ bilirubin, and to release free iron. Up-regulation of HO-1 lowers blood pressure in animals. However, the underlying mechanism is still unknown. The present study was designed to investigate whether or not up-regulation of HO-1 by the pharmacological agent hemin improves endothelial function in arteries of the spontaneous hypertensive rat (SHR). METHODS: 36 weeks old SHR were divided into a hemin treatment (50 mg•kg-1, i.p., 1 d) and a control group (normal saline). Rings of aorta and mesenteric arteries were isolated for isometric tension recording, measurement of the intracellular reactive oxygen species (ROS) and prostanoids, and measurement of protein expression. RESULTS: The hemin treatment augmented the expression of HO-1 in the aorta and impaired both acetylcholine- and A23187-induced endothelium-dependent contractions. ROS production was suppressed, which could be explained by a lower expression of Nox2 and COX-1; the production of prostacyclin was decreased, which was explained by a lower expression of COX-1; contractions to vasoconstrictor concentrations of prostacyclin and its mimetic iloprost were attenuated, suggesting that the responsiveness of thromboxane-prostanoid (TP) receptors to prostacyclin was decreased. The suppression of ROS and prostacyclin, as well as the decrease of TP receptors sensitivity, concur to explain the impairment of endothelium-dependent contractions caused by hemin treatment. In mesenteric arteries, hemin treatment potentiated acetylcholine-evoked relaxations attributable to endothelium-dependent hyperpolarizations (EDHF-mediated) in the presence of L-NAME and indomethacin. The IK channel blocker TRAM-34 and the Na+-K+-ATPase channel blocker ouabain significantly impaired these hemin-potentiated relaxations; K+-mediated relaxations and expression of Na+-K+-ATPase were significantly increased by hemin treatment, explaining the improved EDHF-mediated relaxations by HO-1 induction. CONCLUSION: Up-regulation of HO-1 improves endothelial function by attenuating endothelium-dependent contractions and potentiating endothelium-dependent hyperpolarizations.
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/10722/149236
ISSN
2015 SCImago Journal Rankings: 0.119

 

DC FieldValueLanguage
dc.contributor.authorLi, Z-
dc.contributor.authorVanhoutte, PM-
dc.date.accessioned2012-06-22T06:32:02Z-
dc.date.available2012-06-22T06:32:02Z-
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. 138-
dc.identifier.issn1000-3002-
dc.identifier.urihttp://hdl.handle.net/10722/149236-
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: Heme oxygenase (HO) attenuates the production of reactive oxygen species (ROS) by its ability to degrade heme and produce carbon monoxide (CO), biliverdin/ bilirubin, and to release free iron. Up-regulation of HO-1 lowers blood pressure in animals. However, the underlying mechanism is still unknown. The present study was designed to investigate whether or not up-regulation of HO-1 by the pharmacological agent hemin improves endothelial function in arteries of the spontaneous hypertensive rat (SHR). METHODS: 36 weeks old SHR were divided into a hemin treatment (50 mg•kg-1, i.p., 1 d) and a control group (normal saline). Rings of aorta and mesenteric arteries were isolated for isometric tension recording, measurement of the intracellular reactive oxygen species (ROS) and prostanoids, and measurement of protein expression. RESULTS: The hemin treatment augmented the expression of HO-1 in the aorta and impaired both acetylcholine- and A23187-induced endothelium-dependent contractions. ROS production was suppressed, which could be explained by a lower expression of Nox2 and COX-1; the production of prostacyclin was decreased, which was explained by a lower expression of COX-1; contractions to vasoconstrictor concentrations of prostacyclin and its mimetic iloprost were attenuated, suggesting that the responsiveness of thromboxane-prostanoid (TP) receptors to prostacyclin was decreased. The suppression of ROS and prostacyclin, as well as the decrease of TP receptors sensitivity, concur to explain the impairment of endothelium-dependent contractions caused by hemin treatment. In mesenteric arteries, hemin treatment potentiated acetylcholine-evoked relaxations attributable to endothelium-dependent hyperpolarizations (EDHF-mediated) in the presence of L-NAME and indomethacin. The IK channel blocker TRAM-34 and the Na+-K+-ATPase channel blocker ouabain significantly impaired these hemin-potentiated relaxations; K+-mediated relaxations and expression of Na+-K+-ATPase were significantly increased by hemin treatment, explaining the improved EDHF-mediated relaxations by HO-1 induction. CONCLUSION: Up-regulation of HO-1 improves endothelial function by attenuating endothelium-dependent contractions and potentiating endothelium-dependent hyperpolarizations.-
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.titleUp-regulation of heme oxygenase-1 improves endothelial function in the spontaneous hypertensive rat-
dc.typeConference_Paper-
dc.identifier.emailVanhoutte, PM: vanhoutt@hku.hk-
dc.identifier.authorityVanhoutte, PM=rp00238-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros200014-
dc.identifier.volume25-
dc.identifier.issue增刊-
dc.identifier.spage138-
dc.identifier.epage138-
dc.publisher.placeBeijing, China-

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