Acute effects of bradykinin on cerebral microvascular permeability in the anaesthetized rat

Hdl Handle:
http://hdl.handle.net/10149/99233
Title:
Acute effects of bradykinin on cerebral microvascular permeability in the anaesthetized rat
Authors:
Sarker, M. H. (Mosharraf); Hu, D-E. (De-En); Fraser, P. A. (Paul)
Affiliation:
King's College London. Centre for Cardiovascular Biology and Medicine.
Citation:
Sarker, M. H., Hu, D-E. and Fraser, P. A. (2000) 'Acute effects of bradykinin on cerebral microvascular permeability in the anaesthetized rat', The Journal of Physiology, 528 (1), pp.177-187.
Publisher:
Wiley-Blackwell
Journal:
The Journal of Physiology
Issue Date:
1-Oct-2000
URI:
http://hdl.handle.net/10149/99233
DOI:
10.1111/j.1469-7793.2000.00177.x
Abstract:
1. The permeability response to acutely applied bradykinin and [des-Arg9]-bradykinin on single cerebral venular capillaries has been investigated using the low molecular mass fluorescent dyes Lucifer Yellow and Sulforhodamine B with the single vessel occlusion technique. 2. When bradykinin was applied repeatedly for up to 2 h, the permeability increase was small and reversible for concentrations that ranged from 5 nM to 50 μM. 3. The log EC50 of the permeability response to bradykinin was -5·3 ± 0·15 (logM; mean ± S.E.M.). This was reduced to -6·37 ± 0·24 with the angiotensin-converting enzyme inhibitor captopril, to -6·33 ± 0·19 with the neutral endopeptidase inhibitor phosphoramidon and to -7·3 ± 0·20 with captopril and phosphoramidon combined. 4. The permeability response to bradykinin was blocked by the bradykinin B2 receptor antagonist HOE 140, by inhibition of the Ca2+-independent phospholipase A2, by the scavenging of free radicals, or by inhibition of both cyclo-oxygenase and lipoxygenase in combination. Block of Ca2+ entry channels with SKF 96365 had no effect on the response. 5. Application of [des-Arg9]-bradykinin also increased permeability over the concentration range 5 nM to 50 μM, with a log EC50 of -5·6 ± 0·37. This response was not affected by free radical scavenging, but was completely blocked by the histamine H2 receptor blocker cimetidine. 6. These results imply that the acute permeability response to bradykinin is mediated via the release of arachidonic acid, which is acted on by cyclo-oxygenase and lipoxygenase resulting in the formation of free radicals, and that the response to [des-Arg9]-bradykinin is mediated via histamine.
Type:
Article
Language:
en
Keywords:
bradykinin; cerebral microvascular permeability; anaesthetized rat; animal experiment; histamine; fluorescent dye
ISSN:
0022-3751; 1469-7793
Rights:
Subject to restrictions, author can archive post-print (ie final draft post-refereeing). For full details see http://www.sherpa.ac.uk/romeo/ [Accessed 19/05/2010]
Citation Count:
14 [Scopus, 19/05/2010]

Full metadata record

DC FieldValue Language
dc.contributor.authorSarker, M. H. (Mosharraf)en
dc.contributor.authorHu, D-E. (De-En)en
dc.contributor.authorFraser, P. A. (Paul)en
dc.date.accessioned2010-05-19T07:55:41Z-
dc.date.available2010-05-19T07:55:41Z-
dc.date.issued2000-10-01-
dc.identifier.citationThe Journal of Physiology; 528(1):177-187en
dc.identifier.issn0022-3751-
dc.identifier.issn1469-7793-
dc.identifier.doi10.1111/j.1469-7793.2000.00177.x-
dc.identifier.urihttp://hdl.handle.net/10149/99233-
dc.description.abstract1. The permeability response to acutely applied bradykinin and [des-Arg9]-bradykinin on single cerebral venular capillaries has been investigated using the low molecular mass fluorescent dyes Lucifer Yellow and Sulforhodamine B with the single vessel occlusion technique. 2. When bradykinin was applied repeatedly for up to 2 h, the permeability increase was small and reversible for concentrations that ranged from 5 nM to 50 μM. 3. The log EC50 of the permeability response to bradykinin was -5·3 ± 0·15 (logM; mean ± S.E.M.). This was reduced to -6·37 ± 0·24 with the angiotensin-converting enzyme inhibitor captopril, to -6·33 ± 0·19 with the neutral endopeptidase inhibitor phosphoramidon and to -7·3 ± 0·20 with captopril and phosphoramidon combined. 4. The permeability response to bradykinin was blocked by the bradykinin B2 receptor antagonist HOE 140, by inhibition of the Ca2+-independent phospholipase A2, by the scavenging of free radicals, or by inhibition of both cyclo-oxygenase and lipoxygenase in combination. Block of Ca2+ entry channels with SKF 96365 had no effect on the response. 5. Application of [des-Arg9]-bradykinin also increased permeability over the concentration range 5 nM to 50 μM, with a log EC50 of -5·6 ± 0·37. This response was not affected by free radical scavenging, but was completely blocked by the histamine H2 receptor blocker cimetidine. 6. These results imply that the acute permeability response to bradykinin is mediated via the release of arachidonic acid, which is acted on by cyclo-oxygenase and lipoxygenase resulting in the formation of free radicals, and that the response to [des-Arg9]-bradykinin is mediated via histamine.en
dc.language.isoenen
dc.publisherWiley-Blackwellen
dc.rightsSubject to restrictions, author can archive post-print (ie final draft post-refereeing). For full details see http://www.sherpa.ac.uk/romeo/ [Accessed 19/05/2010]en
dc.subjectbradykininen
dc.subjectcerebral microvascular permeabilityen
dc.subjectanaesthetized raten
dc.subjectanimal experimenten
dc.subjecthistamineen
dc.subjectfluorescent dyeen
dc.titleAcute effects of bradykinin on cerebral microvascular permeability in the anaesthetized raten
dc.typeArticleen
dc.contributor.departmentKing's College London. Centre for Cardiovascular Biology and Medicine.en
dc.identifier.journalThe Journal of Physiologyen
ref.citationcount14 [Scopus, 19/05/2010]en
or.citation.harvardSarker, M. H., Hu, D-E. and Fraser, P. A. (2000) 'Acute effects of bradykinin on cerebral microvascular permeability in the anaesthetized rat', The Journal of Physiology, 528 (1), pp.177-187.-
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