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Conference Paper: Thymoquinone as a pharmacological tool to study the endothelium-dependent, soluble guanylyl cyclase-dependent augmentation caused by hypoxia in isolated arteries

TitleThymoquinone as a pharmacological tool to study the endothelium-dependent, soluble guanylyl cyclase-dependent augmentation caused by hypoxia in isolated arteries
Authors
KeywordsPharmacy and pharmacology environmental studies
Toxicology and environmental safety
Issue Date2014
PublisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/PTO
Citation
The 17th World Congress of Basic and Clinical Pharmacology (WCP2014), Cape Town, South Africa, 13-18 July 2014. In Basic & Clinical Pharmacology & Toxicology, 2014, v. 115 suppl. s1, p. 50, abstract no. 162 How to Cite?
AbstractBACKGROUND: Experiments were designed to study the effects of thymoquinone on isolated arteries and to determine the mechanism underlying the endothelium-dependent, soluble guanylyl cyclase-dependent augmentation the compound is causing. METHODS: Rings, with or without endothelium, of porcine coronary arteries and rat arteries were suspended in conventional organ chambers for isometric tension recording. Certain rings were incubated with inhibitors of nitric oxide (NO) synthase (L-NG-nitroarginine methyl ester, L-NAME) or soluble guanylyl cyclase (1H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one, ODQ). They were contracted with phenylephrine (rat arteries) or prostaglandin F2a (porcine coronaries) and exposed to increasing concentrations of thymoquinone. Cyclic nucleotides were measured by HPLC-MS/MS. RESULTS: Thymoquinone caused a sustained further increase of tension in rings with endothelium. This augmentation was prevented by endothelium-removal, L-NAME and ODQ. Thymoquinone did not change the tissue levels of cyclic GMP, measured by immunoassay. Incubation with the NO-donor DETA NONOate in L-NAME-treated rings restored and even increased the contractile response to thymoquinone. Treatment with 8-bromo cyclic GMP or pyrophospate did not restore the augmentation by thymoquinone. By contrast, administration of cyclic IMP restored contractions to thymoquinone in rings without endothelium. HPLC-MS/MS measurements revealed that the compound increased the production of cyclic IMP. CONCLUSIONS: The endothelium-dependent augmentation caused by thymoquinone requires endothelium-derived NO and activation of soluble guanylyl cyclase, as described under hypoxic conditions. In addition, both thymoquinone- and hypoxia-induced augmentation require production of cyclic IMP but not the presence of either pyrophosphate or cyclic GMP. Thus, thymoquinone can serve as a pharmacological tool to mimic the endothelium-dependent vasoconstrictor effects of intermittent hypoxia, as seen in the clinical setting of sleep apnea patients.
DescriptionSession - Cardiovascular Pharmacology
This journal suppl. entitled: Special Issue: Abstracts of the 17th World Congress of Basic and Clinical Pharmacology ... 2014
Persistent Identifierhttp://hdl.handle.net/10722/201276
ISSN
2015 Impact Factor: 3.097
2015 SCImago Journal Rankings: 0.539

 

DC FieldValueLanguage
dc.contributor.authorDetremmerie, CMSen_US
dc.contributor.authorLeung, Sen_US
dc.contributor.authorXu, Aen_US
dc.contributor.authorAlkharfy, Ken_US
dc.contributor.authorGao, Yen_US
dc.contributor.authorVanhoutte, Pen_US
dc.date.accessioned2014-08-21T07:20:17Z-
dc.date.available2014-08-21T07:20:17Z-
dc.date.issued2014en_US
dc.identifier.citationThe 17th World Congress of Basic and Clinical Pharmacology (WCP2014), Cape Town, South Africa, 13-18 July 2014. In Basic & Clinical Pharmacology & Toxicology, 2014, v. 115 suppl. s1, p. 50, abstract no. 162en_US
dc.identifier.issn1742-7835-
dc.identifier.urihttp://hdl.handle.net/10722/201276-
dc.descriptionSession - Cardiovascular Pharmacology-
dc.descriptionThis journal suppl. entitled: Special Issue: Abstracts of the 17th World Congress of Basic and Clinical Pharmacology ... 2014-
dc.description.abstractBACKGROUND: Experiments were designed to study the effects of thymoquinone on isolated arteries and to determine the mechanism underlying the endothelium-dependent, soluble guanylyl cyclase-dependent augmentation the compound is causing. METHODS: Rings, with or without endothelium, of porcine coronary arteries and rat arteries were suspended in conventional organ chambers for isometric tension recording. Certain rings were incubated with inhibitors of nitric oxide (NO) synthase (L-NG-nitroarginine methyl ester, L-NAME) or soluble guanylyl cyclase (1H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one, ODQ). They were contracted with phenylephrine (rat arteries) or prostaglandin F2a (porcine coronaries) and exposed to increasing concentrations of thymoquinone. Cyclic nucleotides were measured by HPLC-MS/MS. RESULTS: Thymoquinone caused a sustained further increase of tension in rings with endothelium. This augmentation was prevented by endothelium-removal, L-NAME and ODQ. Thymoquinone did not change the tissue levels of cyclic GMP, measured by immunoassay. Incubation with the NO-donor DETA NONOate in L-NAME-treated rings restored and even increased the contractile response to thymoquinone. Treatment with 8-bromo cyclic GMP or pyrophospate did not restore the augmentation by thymoquinone. By contrast, administration of cyclic IMP restored contractions to thymoquinone in rings without endothelium. HPLC-MS/MS measurements revealed that the compound increased the production of cyclic IMP. CONCLUSIONS: The endothelium-dependent augmentation caused by thymoquinone requires endothelium-derived NO and activation of soluble guanylyl cyclase, as described under hypoxic conditions. In addition, both thymoquinone- and hypoxia-induced augmentation require production of cyclic IMP but not the presence of either pyrophosphate or cyclic GMP. Thus, thymoquinone can serve as a pharmacological tool to mimic the endothelium-dependent vasoconstrictor effects of intermittent hypoxia, as seen in the clinical setting of sleep apnea patients.-
dc.languageengen_US
dc.publisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/PTO-
dc.relation.ispartofBasic & Clinical Pharmacology & Toxicologyen_US
dc.rightsThe definitive version is available at www.blackwell-synergy.com-
dc.subjectPharmacy and pharmacology environmental studies-
dc.subjectToxicology and environmental safety-
dc.titleThymoquinone as a pharmacological tool to study the endothelium-dependent, soluble guanylyl cyclase-dependent augmentation caused by hypoxia in isolated arteriesen_US
dc.typeConference_Paperen_US
dc.identifier.emailLeung, S: swsleung@hku.hken_US
dc.identifier.emailXu, A: amxu@hkucc.hku.hken_US
dc.identifier.emailVanhoutte, P: vanhoutt@hku.hken_US
dc.identifier.authorityLeung, S=rp00235en_US
dc.identifier.authorityXu, A=rp00485en_US
dc.identifier.authorityVanhoutte, P=rp00238en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1111/bcpt.12259_1-
dc.identifier.hkuros233053en_US
dc.identifier.volume115-
dc.identifier.issuesuppl. s1-
dc.identifier.spage50, abstract no. 162-
dc.identifier.epage50, abstract no. 162-
dc.publisher.placeUnited Kingdom-

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