File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Interaction of vasoactive substances released by platelet-activating factor in the rat perfused heart

TitleInteraction of vasoactive substances released by platelet-activating factor in the rat perfused heart
Authors
Issue Date1991
PublisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1
Citation
British Journal Of Pharmacology, 1991, v. 104 n. 4, p. 933-937 How to Cite?
Abstract1. The coronary vascular effects of platelet-activating factor (PAF) have been intensively studied and it has been proposed that they are mediated by the release of vasoactive substances. In this study, a cascade perfusion model using two rat perfused hearts was developed to investigate the properties of PAF-released vasoactive substances and the interplay of these substances. The properties of the vasoactive substances after an injection of PAF (100 pmol) in the rat perfused heart were examined by collecting the effluent from the first heart for the perfusion of a second (recipient) heart. The presence of vasoconstrictor substances in the effluent was characterized by an increase in the perfusion pressure of the recipient heart. 2. Previous exposure of the recipient heart of PAF (100 pmol) abolished the response of the heart to subsequent administration of PAF, but did not affect the response of the recipient heart to the effluent. This suggested that the coronary vasoconstrictor response of the recipient heart was not due to the presence of PAF in the effluent but to other vasoactive substances. 3. Pretreatment of the recipient heart with the leukotriene receptor antagonist, L-649,923 (5 μM), partially reduced the vasoconstrictor effect of the effluent. Pretreatment of the first heart with indomethacin (2.8 μM) also partially reduced the vasoconstrictor effect of the effluent. The combination of indomethacin pretreatment of the first heart and L-649,923 pretreatment of the recipient heart completely abolished the vasoconstrictor effect of the effluent suggesting that both prostaglandins and leukotrienes are involved in the vasoconstrictor effect of the effluent. 4. Pretreatment of both hearts with L-649,923 or the first heart with the leukotriene synthesis inhibitor (MK-886, 10 μM) completely abolished the vasoconstrictor effect of the effluent. This suggested that the indomethacin sensitive vasoconstrictor component of the effluent might be regulated by leukotrienes in the first heart. However, infusion of leukotrienes (LTB4, LTC4 and LTD4) to the first heart did not reproduce this vasoconstrictor component of the effluent in the recipient heart. 5. In conclusion, our study demonstrated through the use of a leukotriene receptor antagonist, a leukotriene synthesis inhibitor and a cyclo-oxygenase inhibitor that the vasoconstrictor effect of the effluent of the rat perfused heart after an injection of PAF is mediated by leukotrienes and prostaglandins. The ability of leukotriene receptor blockade and inhibition of leukotriene synthesis to mimic the effect of indomethacin indicates that the production and/or release of cyclo-oxygenase products in the effluent by PAF can be modulated by leukotrienes. The inability of exogenously applied leukotrienes to modulate the production and/or the release of cyclo-oxygenase products in the effluent suggests that the PAF-induced production of prostaglandins may be mediated by intracellular leukotrienes or at sites not accessible to exogenously applied leukotrienes.
Persistent Identifierhttp://hdl.handle.net/10722/171002
ISSN
2015 Impact Factor: 5.259
2015 SCImago Journal Rankings: 2.368
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHu, Wen_US
dc.contributor.authorMan, RYKen_US
dc.date.accessioned2012-10-30T06:11:47Z-
dc.date.available2012-10-30T06:11:47Z-
dc.date.issued1991en_US
dc.identifier.citationBritish Journal Of Pharmacology, 1991, v. 104 n. 4, p. 933-937en_US
dc.identifier.issn0007-1188en_US
dc.identifier.urihttp://hdl.handle.net/10722/171002-
dc.description.abstract1. The coronary vascular effects of platelet-activating factor (PAF) have been intensively studied and it has been proposed that they are mediated by the release of vasoactive substances. In this study, a cascade perfusion model using two rat perfused hearts was developed to investigate the properties of PAF-released vasoactive substances and the interplay of these substances. The properties of the vasoactive substances after an injection of PAF (100 pmol) in the rat perfused heart were examined by collecting the effluent from the first heart for the perfusion of a second (recipient) heart. The presence of vasoconstrictor substances in the effluent was characterized by an increase in the perfusion pressure of the recipient heart. 2. Previous exposure of the recipient heart of PAF (100 pmol) abolished the response of the heart to subsequent administration of PAF, but did not affect the response of the recipient heart to the effluent. This suggested that the coronary vasoconstrictor response of the recipient heart was not due to the presence of PAF in the effluent but to other vasoactive substances. 3. Pretreatment of the recipient heart with the leukotriene receptor antagonist, L-649,923 (5 μM), partially reduced the vasoconstrictor effect of the effluent. Pretreatment of the first heart with indomethacin (2.8 μM) also partially reduced the vasoconstrictor effect of the effluent. The combination of indomethacin pretreatment of the first heart and L-649,923 pretreatment of the recipient heart completely abolished the vasoconstrictor effect of the effluent suggesting that both prostaglandins and leukotrienes are involved in the vasoconstrictor effect of the effluent. 4. Pretreatment of both hearts with L-649,923 or the first heart with the leukotriene synthesis inhibitor (MK-886, 10 μM) completely abolished the vasoconstrictor effect of the effluent. This suggested that the indomethacin sensitive vasoconstrictor component of the effluent might be regulated by leukotrienes in the first heart. However, infusion of leukotrienes (LTB4, LTC4 and LTD4) to the first heart did not reproduce this vasoconstrictor component of the effluent in the recipient heart. 5. In conclusion, our study demonstrated through the use of a leukotriene receptor antagonist, a leukotriene synthesis inhibitor and a cyclo-oxygenase inhibitor that the vasoconstrictor effect of the effluent of the rat perfused heart after an injection of PAF is mediated by leukotrienes and prostaglandins. The ability of leukotriene receptor blockade and inhibition of leukotriene synthesis to mimic the effect of indomethacin indicates that the production and/or release of cyclo-oxygenase products in the effluent by PAF can be modulated by leukotrienes. The inability of exogenously applied leukotrienes to modulate the production and/or the release of cyclo-oxygenase products in the effluent suggests that the PAF-induced production of prostaglandins may be mediated by intracellular leukotrienes or at sites not accessible to exogenously applied leukotrienes.en_US
dc.languageengen_US
dc.publisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1en_US
dc.relation.ispartofBritish Journal of Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshArachidonic Acids - Physiologyen_US
dc.subject.meshBlood Gas Analysisen_US
dc.subject.meshCoronary Circulation - Drug Effects - Physiologyen_US
dc.subject.meshCyclooxygenase Inhibitors - Pharmacologyen_US
dc.subject.meshHeart - Drug Effectsen_US
dc.subject.meshIndoles - Pharmacologyen_US
dc.subject.meshIndomethacin - Pharmacologyen_US
dc.subject.meshLeukotriene Antagonistsen_US
dc.subject.meshPerfusionen_US
dc.subject.meshPhenylbutyrates - Pharmacologyen_US
dc.subject.meshPlatelet Activating Factor - Antagonists & Inhibitors - Pharmacologyen_US
dc.subject.meshPotassium - Blooden_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Inbred Strainsen_US
dc.subject.meshSrs-A - Antagonists & Inhibitorsen_US
dc.subject.meshSodium - Blooden_US
dc.subject.meshVasoconstriction - Drug Effectsen_US
dc.titleInteraction of vasoactive substances released by platelet-activating factor in the rat perfused hearten_US
dc.typeArticleen_US
dc.identifier.emailMan, RYK:rykman@hkucc.hku.hken_US
dc.identifier.authorityMan, RYK=rp00236en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1111/j.1476-5381.1991.tb12529.x-
dc.identifier.pmid1810604-
dc.identifier.scopuseid_2-s2.0-0025748039en_US
dc.identifier.volume104en_US
dc.identifier.issue4en_US
dc.identifier.spage933en_US
dc.identifier.epage937en_US
dc.identifier.isiWOS:A1991GT19000027-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridHu, W=7404360099en_US
dc.identifier.scopusauthoridMan, RYK=7004986435en_US

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats