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

Mosharraf Sarker, D. E. Hu, P. A. Fraser

    Research output: Contribution to journalArticle

    36 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)177-187
    Number of pages11
    JournalJournal of Physiology
    Volume528
    Issue number1
    DOIs
    Publication statusPublished - 1 Oct 2000

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