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

M H Sarker, D E Hu, P A Fraser

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

Abstract

1. The permeability response to acutely applied bradykinin and [des-Arg(9)]-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 muM. 3. The logEC(50) 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 B-2 receptor antagonist HOE 140, by inhibition of the Ca2+-independent phospholipase A(2), by the scavenging of free radicals, or by inhibition of both cyclo-oxygenase and lipoxygenase in combination. Block of Ca2+ entry channels with SWP 96365 had no effect on the response. 5. Application of [des-Arg(9)] bradykinin also increased permeability over the concentration range 5 nM to 50 muM, with a logEC(50) of -5.6 +/- 0.37. This response was not affected by free radical scavenging, but was completely blocked by the histamine H-2 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-Arg(9)]-bradykinin is mediated via histamine.
Original languageEnglish
Pages (from-to)177 - 187
Number of pages11
JournalThe Journal of Physiology
Volume528
Issue number1
DOIs
Publication statusPublished - 1 Oct 2000

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